Receptor (biochemistry)
Encyclopedia
In biochemistry
, a receptor is a molecule
found on the surface of a cell
, which receives specific chemical signals from neighbouring cells or the wider environment within an organism. These signals tell a cell to do something—for example to divide or die, or to allow certain molecules to enter or exit the cell.
Receptors are protein
molecules, embedded in either the plasma membrane (cell surface receptors) or the cytoplasm
(nuclear receptor
s) of a cell, to which one or more specific kinds of signaling
molecules may attach. A molecule which binds (attaches) to a receptor is called a ligand
, and may be a peptide
(short protein) or other small molecule, such as a neurotransmitter
, a hormone
, a pharmaceutical drug, or a toxin. Each kind of receptor can bind only certain ligand shapes. Each cell typically has many receptors, of many different kinds. Simply put, a receptor functions as a keyhole that opens a biochemical pathway when the proper ligand is inserted.
Ligand binding stabilizes a certain receptor conformation
(the three-dimensional shape of the receptor protein, with no change in sequence). This is often associated with gain of or loss of protein activity, ordinarily leading to some sort of cellular response. However, some ligands (e.g. antagonists
) merely block receptors without inducing any response. Ligand-induced changes in receptors result in cellular changes which constitute the biological activity of the ligands. Many functions of the human body are regulated by these receptors responding uniquely to specific molecules like this.
, dual polarisation interferometry
, computer modelling
, and structure-function studies, which have advanced the understanding of drug action
at the binding sites of receptors. Structure activity relationships correlate induced conformational changes with biomolecular activity, and are studied using dynamic techniques such as circular dichroism
and dual polarisation interferometry
.
Depending on their functions and ligands
, several types of receptors may be identified:
Membrane receptors are isolated from cell membranes by complex extraction procedures using solvents
, detergents, and/or affinity purification.
process. Ligands bind to receptors and dissociate from them according to the law of mass action.
One measure of how well a molecule fits a receptor is the binding affinity, which is inversely related to the dissociation constant
Kd. A good fit corresponds with high affinity and low Kd. The final biological response (e.g. second messenger cascade
, muscle contraction), is only achieved after a significant number of receptors are activated.
The receptor-ligand affinity is greater than enzyme-substrate affinity. Whilst both interactions are specific and reversible, there is no chemical modification of the ligand as seen with the substrate upon binding to its enzyme.
If the receptor exists in two states (see this picture), then the ligand binding must account for these two receptor states. For a more detailed discussion of two-state binding, which is thought to occur as an activation mechanism in many receptors see this link.
binding. Mutations in receptors that result in increased constitutive activity underlie some inherited diseases, such as precocious puberty (due to mutations in luteinizing hormone receptors) and hyperthyroidism (due to mutations in thyroid-stimulating hormone receptors). For the use of statistical mechanics
in a quantitative study of the
ligand-receptor binding affinity, see the comprehensive article on the configuration integral.
Drug effect is directly proportional to number of receptors occupied.
Drug effect ceases as drug-receptor complex dissociate
Ariens & Stephenson theory
introduced Terms of "affinity" & "efficacy"
Affinity: ability of the drug to combine with receptor to create drug-receptor complex
Efficacy: ability of the drug-receptor complex to initiate a response
Affinity “drug-receptor interaction” is governed by the law of mass action.
In this theory
Agonist: drug with high affinity & high intrinsic activity
Partial agonist: drug with high affinity & low intrinsic activity
Antagonist: drug with high affinity & low intrinsic activity
Rate theory
The activation of receptors is directly proportional to the total number of encounters of the drug with its receptors per unit time
Pharmacological activity is directly proportional to the rate of dissociation & association not number of receptors occupied
Agonist:drug with fast association & fast dissociation
Partial agonist:drug with intermediate association & intermediate dissociation
Antagonist:drug with fast association & slow dissociation
Induced fit theory
As the drug approaches the receptor the receptor alters the conformation of its binding site to produce drug—receptor complex
.
many more ...
of their intracellular domains.
This family of receptors includes;
oligomers. They are receptors that respond to extracellular ligands and receptors that respond to intracellular ligands.
The entire repertoire of human plasma membrane receptors is listed at the Human Plasma Membrane Receptome (http://www.receptome.org).
s involve hereditary defects in receptor genes. Often, it is hard to determine whether the receptor is nonfunctional or the hormone
is produced at decreased level; this gives rise to the "pseudo-hypo-" group of endocrine disorders
, where there appears to be a decreased hormonal level while in fact it is the receptor that is not responding sufficiently to the hormone.
or neurotransmitter
to alter its sensitivity to this molecule. This is a locally acting feedback
mechanism.
Receptor desensitization
are pattern recognition receptors (PRRs), toll-like receptor
s (TLRs), killer activated and killer inhibitor receptors (KARs and KIRs), complement receptor
s, Fc receptors, B cell receptors and T cell receptor
s.
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
, a receptor is a molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
found on the surface of a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, which receives specific chemical signals from neighbouring cells or the wider environment within an organism. These signals tell a cell to do something—for example to divide or die, or to allow certain molecules to enter or exit the cell.
Receptors are protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
molecules, embedded in either the plasma membrane (cell surface receptors) or the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
(nuclear receptor
Nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...
s) of a cell, to which one or more specific kinds of signaling
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
molecules may attach. A molecule which binds (attaches) to a receptor is called a ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
, and may be a peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
(short protein) or other small molecule, such as a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
, a hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
, a pharmaceutical drug, or a toxin. Each kind of receptor can bind only certain ligand shapes. Each cell typically has many receptors, of many different kinds. Simply put, a receptor functions as a keyhole that opens a biochemical pathway when the proper ligand is inserted.
Ligand binding stabilizes a certain receptor conformation
Conformational change
A macromolecule is usually flexible and dynamic. It can change its shape in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change...
(the three-dimensional shape of the receptor protein, with no change in sequence). This is often associated with gain of or loss of protein activity, ordinarily leading to some sort of cellular response. However, some ligands (e.g. antagonists
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
) merely block receptors without inducing any response. Ligand-induced changes in receptors result in cellular changes which constitute the biological activity of the ligands. Many functions of the human body are regulated by these receptors responding uniquely to specific molecules like this.
Structure
The shapes and actions of receptors are studied by X-ray crystallographyX-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
, dual polarisation interferometry
Dual Polarisation Interferometry
Dual polarization interferometry is an analytical technique that can probe molecular scale layers adsorbed to the surface of a waveguide by using the evanescent wave of a laser beam confined to the waveguide...
, computer modelling
Computer simulation
A computer simulation, a computer model, or a computational model is a computer program, or network of computers, that attempts to simulate an abstract model of a particular system...
, and structure-function studies, which have advanced the understanding of drug action
Drug action
The action of drugs on the human body is called pharmacodynamics, and what the body does with the drug is called pharmacokinetics. The drugs that enter the human tend to stimulate certain receptors, ion channels, act on enzymes or transporter proteins...
at the binding sites of receptors. Structure activity relationships correlate induced conformational changes with biomolecular activity, and are studied using dynamic techniques such as circular dichroism
Circular dichroism
Circular dichroism refers to the differential absorption of left and right circularly polarized light. This phenomenon was discovered by Jean-Baptiste Biot, Augustin Fresnel, and Aimé Cotton in the first half of the 19th century. It is exhibited in the absorption bands of optically active chiral...
and dual polarisation interferometry
Dual Polarisation Interferometry
Dual polarization interferometry is an analytical technique that can probe molecular scale layers adsorbed to the surface of a waveguide by using the evanescent wave of a laser beam confined to the waveguide...
.
Depending on their functions and ligands
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
, several types of receptors may be identified:
- Some receptor proteins are peripheral membrane proteinPeripheral membrane proteinPeripheral membrane proteins are proteins that adhere only temporarily to the biological membrane with which they are associated. These molecules attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and...
s. - Many hormoneHormone receptorA hormone receptor is a receptor protein on the surface of a cell or in its interior that binds to a specific hormone. The hormone causes many changes to take place in the cell....
and neurotransmitter receptorNeurotransmitter receptorA Neurotransmitter receptor is a membrane receptor protein that is activated by a Neurotransmitter. A membrane protein interacts with the lipid bilayer that encloses the cell and a membrane receptor protein interacts with a chemical in the cells external environment, which binds to the cell...
s are transmembrane proteins: transmembrane receptors are embedded in the phospholipid bilayer of cell membraneCell membraneThe cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s, that allow the activation of signal transductionSignal transductionSignal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
pathways in response to the activation by the binding molecule, or ligandLigand (biochemistry)In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
.- Metabotropic receptorMetabotropic receptorMetabotropic receptor is a subtype of membrane receptors at the surface or in vesicles of eukaryotic cells.In the nervous system, based on their structural and functional characteristics, neurotransmitter receptors can be classified into two broad categories: metabotropic and ionotropic receptors...
s are coupled to G proteinG proteinG proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
s and affect the cell indirectly through enzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s which control ion channelIon channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s. - Ionotropic receptors (also known as ligand-gated ion channelLigand-gated ion channelLigand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger , such as a neurotransmitter.The binding site of endogenous ligands on LGICs...
s) contain a central pore which opens in response to the binding of ligand.
- Metabotropic receptor
- Another major class of receptors are intracellularIntracellularNot to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
proteins such as those for steroidSteroidA steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
and intracrineIntracrineIntracrine refers to a hormone that acts inside a cell. Steroid hormones act through intracellular receptors and, thus, may be considered to be intracrines. In contrast, peptide or protein hormones, in general, act as endocrines, autocrines, or paracrines by binding to their receptors present on...
peptide hormonePeptide hormonePeptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...
receptors. These receptors often can enter the cell nucleusCell nucleusIn cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
and modulate gene expressionGene expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
in response to the activation by the ligand.
Membrane receptors are isolated from cell membranes by complex extraction procedures using solvents
Liquid-liquid extraction
Liquid–liquid extraction, also known as solvent extraction and partitioning, is a method to separate compounds based on their relative solubilities in two different immiscible liquids, usually water and an organic solvent. It is an extraction of a substance from one liquid phase into another liquid...
, detergents, and/or affinity purification.
Binding and activation
Ligand binding is an equilibriumChemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...
process. Ligands bind to receptors and dissociate from them according to the law of mass action.
- (the brackets stand for concentrations)
One measure of how well a molecule fits a receptor is the binding affinity, which is inversely related to the dissociation constant
Dissociation constant
In chemistry, biochemistry, and pharmacology, a dissociation constant is a specific type of equilibrium constant that measures the propensity of a larger object to separate reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into...
Kd. A good fit corresponds with high affinity and low Kd. The final biological response (e.g. second messenger cascade
Second messenger system
Second messengers are molecules that relay signals from receptors on the cell surface to target molecules inside the cell, in the cytoplasm or nucleus. They relay the signals of hormones like epinephrine , growth factors, and others, and cause some kind of change in the activity of the cell...
, muscle contraction), is only achieved after a significant number of receptors are activated.
The receptor-ligand affinity is greater than enzyme-substrate affinity. Whilst both interactions are specific and reversible, there is no chemical modification of the ligand as seen with the substrate upon binding to its enzyme.
If the receptor exists in two states (see this picture), then the ligand binding must account for these two receptor states. For a more detailed discussion of two-state binding, which is thought to occur as an activation mechanism in many receptors see this link.
Constitutive activity
A receptor which is capable of producing its biological response in the absence of a bound ligand is said to display "constitutive activity". The constitutive activity of receptors may be blocked by inverse agonistInverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....
binding. Mutations in receptors that result in increased constitutive activity underlie some inherited diseases, such as precocious puberty (due to mutations in luteinizing hormone receptors) and hyperthyroidism (due to mutations in thyroid-stimulating hormone receptors). For the use of statistical mechanics
Statistical mechanics
Statistical mechanics or statistical thermodynamicsThe terms statistical mechanics and statistical thermodynamics are used interchangeably...
in a quantitative study of the
ligand-receptor binding affinity, see the comprehensive article on the configuration integral.
Theories of drug receptor interaction
Occupation theoryDrug effect is directly proportional to number of receptors occupied.
Drug effect ceases as drug-receptor complex dissociate
Ariens & Stephenson theory
introduced Terms of "affinity" & "efficacy"
Affinity: ability of the drug to combine with receptor to create drug-receptor complex
Efficacy: ability of the drug-receptor complex to initiate a response
Affinity “drug-receptor interaction” is governed by the law of mass action.
In this theory
Agonist: drug with high affinity & high intrinsic activity
Partial agonist: drug with high affinity & low intrinsic activity
Antagonist: drug with high affinity & low intrinsic activity
Rate theory
The activation of receptors is directly proportional to the total number of encounters of the drug with its receptors per unit time
Pharmacological activity is directly proportional to the rate of dissociation & association not number of receptors occupied
Agonist:drug with fast association & fast dissociation
Partial agonist:drug with intermediate association & intermediate dissociation
Antagonist:drug with fast association & slow dissociation
Induced fit theory
As the drug approaches the receptor the receptor alters the conformation of its binding site to produce drug—receptor complex
Agonists versus antagonists
Not every ligand that binds to a receptor also activates the receptor. The following classes of ligands exist:- (Full) agonistAgonistAn agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
s are able to activate the receptor and result in a maximal biological response. Most natural ligands are full agonists. - Partial agonists do not activate receptors thoroughly, causing responses which are partial compared to those of full agonists.
- AntagonistsReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
bind to receptors but do not activate them. This results in receptor blockage, inhibiting the binding of other agonists. - Inverse agonists reduce the activity of receptors by inhibiting their constitutive activity.
Peripheral membrane protein receptors
These receptors are relatively rare compared to the much more common types of receptors that cross the cell membrane. An example of a receptor that is a peripheral membrane protein is the elastin receptorGLB1
Galactosidase, beta 1, also known as GLB1, is a protein which in humans is encoded by the GLB1 gene.The GLB1 protein is a beta-galactosidase that cleaves the terminal beta-galactose from ganglioside substrates and other glycoconjugates...
.
G protein-coupled receptors
These receptors are also known as seven transmembrane receptors or 7TM receptors, because they pass through the membrane seven times.- Muscarinic acetylcholine receptorMuscarinic acetylcholine receptorMuscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
(AcetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
and MuscarineMuscarineMuscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested...
) - Adenosine receptorAdenosine receptorThe adenosine receptors are a class of purinergic receptors, G protein-coupled receptors with adenosine as endogenous ligand.-Pharmacology:...
s (Adenosine) - Adrenoceptors (also known as Adrenergic receptorAdrenergic receptorThe adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
s, for adrenaline, and other structurally related hormoneHormoneA hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s and drugsMedicationA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
) - GABA receptorGABA receptorThe GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
s, Type-B (γ-Aminobutyric acidGamma-aminobutyric acidγ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
or GABA) - Angiotensin receptorAngiotensin receptorThe angiotensin receptors are a class of G protein-coupled receptors with angiotensin II as their ligands. They are important in the renin-angiotensin system: they are responsible for the signal transduction of the vasoconstricting stimulus of the main effector hormone, angiotensin...
s (AngiotensinAngiotensinAngiotensin, a peptide hormone, causes blood vessels to constrict, and drives blood pressure up. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex...
) - Cannabinoid receptorCannabinoid receptorThe cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains...
s (CannabinoidsCannabinoidsCannabinoids are a class of chemical compounds that include the phytocannabinoids , and chemical compounds that mimic the actions of phytocannabinoids or have a similar structure...
) - Cholecystokinin receptorCholecystokinin receptorCholecystokinin receptors or CCK receptors are a group of G-protein coupled receptors which bind the peptide hormones cholecystokinin or gastrin...
s (CholecystokininCholecystokininCholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...
) - Dopamine receptorDopamine receptorDopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
s (DopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
) - Glucagon receptorGlucagon receptorThe glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in activation of adenylate cyclase and increased levels of...
s (GlucagonGlucagonGlucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
) - Melatonin receptorMelatonin receptorA melatonin receptor is a G protein-coupled receptor which binds melatonin.Three types of melatonin receptor have been cloned. The MT1 and MT2 receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype MT3 has been identified in amphibia and...
s (MelatoninMelatoninMelatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
) - Metabotropic glutamate receptorMetabotropic glutamate receptorThe metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs...
s (Glutamate) - Histamine receptorHistamine receptorThe histamine receptors are a class of G protein-coupled receptors with histamine as their endogenous ligand.There are four known histamine receptors:*H1 receptor*H2 receptor*H3 receptor*H4 receptor-Comparison:...
s (HistamineHistamineHistamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
) - Olfactory receptorOlfactory receptorOlfactory receptors expressed in the cell membranes of olfactory receptor neurons are responsible for the detection of odor molecules. Activated olfactory receptors are the initial player in a signal transduction cascade which ultimately produces a nerve impulse which is transmitted to the brain...
s (for the sense of smellOlfactionOlfaction is the sense of smell. This sense is mediated by specialized sensory cells of the nasal cavity of vertebrates, and, by analogy, sensory cells of the antennae of invertebrates...
) - Opioid receptorOpioid receptorOpioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors...
s (OpioidOpioidAn opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
s) - Protease-activated receptorProtease-activated receptorProtease-activated receptors are a subfamily of related G protein-coupled receptors that are activated by cleavage of part of their extracellular domain. They are highly expressed in platelets, but also on endothelial cells, myocytes and neurons....
s - RhodopsinRhodopsinRhodopsin, also known as visual purple, is a biological pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light,...
(a photoreceptor proteinPhotoreceptor proteinPhotoreceptors are light-sensitive proteins involved in the sensing and response to light in a variety of organisms. Some examples are rhodopsin in the photoreceptor cells of the vertebrate retina, phytochrome in plants, and bacteriorhodopsin and bacteriophytochromes in some bacteria...
) - Secretin receptorSecretin receptorHuman secretin receptor is a G protein-coupled receptor which binds secretin and is the leading member of the class B GPCR subfamily.-Interactions:...
s (SecretinSecretinSecretin is a hormone that controls the secretions into the duodenum, and also separately, water homeostasis throughout the body. It is produced in the S cells of the duodenum in the crypts of Lieberkühn...
) - Serotonin receptors, except Type-3 (SerotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, also known as 5-Hydroxytryptamine or 5-HT) - Somatostatin receptorSomatostatin receptorThere are five known somatostatin receptors:* SST1 * SST2 * SST3 * SST4 * SST5 All are G protein-coupled seven transmembrane receptors.-External links:...
s (SomatostatinSomatostatinSomatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
) - Trace-amine associated receptors (Trace amines)
- Calcium-sensing receptorCalcium-sensing receptorThe calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is...
(CalciumCalciumCalcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
) - Chemokine receptors (Chemokines)
many more ...
Receptor tyrosine kinases
These receptors detect ligands and propagate signals via the tyrosine kinaseTyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
of their intracellular domains.
This family of receptors includes;
- Erythropoietin receptorErythropoietin receptorThe erythropoietin receptor is a protein that in humans is encoded by the EPOR gene. EpoR is a 59 kDa peptide and is a member of the cytokine receptor family. EpoR pre-exists as dimers...
(ErythropoietinErythropoietinErythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
) - Insulin receptorInsulin receptorIn molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....
(InsulinInsulinInsulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
) - Eph receptorEph receptorEph receptors are components of cell signalling pathways involved in animal growth and development, forming the largest sub-family of receptor tyrosine kinases . The extracellular domain of an Eph receptor interacts with ephrin ligands, which may be tethered to neighbouring cells...
s - Insulin-like growth factor 1 receptor
- various other growth factorGrowth factor receptorA growth factor receptor is a receptor which binds to growth factor.These receptors may use the JAK/STAT, MAP kinase, and PI3 kinase pathways....
and cytokine receptorCytokine receptorCytokine receptors are receptors that bind cytokines.In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been...
s - ....
Guanylyl cyclase receptors
- GC-A & GC-B: receptors for Atrial-natriuretic peptide (ANP) and other natriuretic peptides
- GC-C: GuanylinGuanylinGuanylin is a 15 amino acid polypeptide that is secreted by goblet cells in the colon. Guanylin acts as an agonist of the guanylyl cyclase receptor GC-C and regulates electrolyte and water transport in intestinal and renal epithelia...
receptor
Ionotropic receptors
Ionotropic receptors are heteromeric or homomericHomomeric
A homomeric substance is one which is made out of any number of identical products or molecules.e.g. A homomeric peptide = glutathione A peptide which is made up of only a single type of amino acid subunit; e.g., alanylalanylalanine.ALA-ALA-ALA...
oligomers. They are receptors that respond to extracellular ligands and receptors that respond to intracellular ligands.
Extracellular ligands
| Receptor | Ligand | Ion current |
| Nicotinic acetylcholine receptor Nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction... |
Acetylcholine Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... , Nicotine Nicotine Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves... |
Na+, K+, Ca2+ |
| Glycine receptor Glycine receptor The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current... (GlyR) |
Glycine Glycine Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid... , Strychnine Strychnine Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion... |
Cl− > HCO−3 |
| GABA receptor GABA receptor The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system... s: GABA-A, GABA-C |
GABA Gabâ Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions... |
Cl− > HCO−3 |
| Glutamate receptor Glutamate receptor Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the... s: NMDA receptor NMDA receptor The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function.... , AMPA receptor AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA... , and Kainate receptor Kainate receptor Kainate receptors, or KARs, are non-NMDA ionotropic receptors which respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug first isolated from red algae Digenea simplex. KARs are less well... |
Glutamate | Na+, K+, Ca2+ |
| 5-HT3 receptor | Serotonin Serotonin Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans... |
Na+, K+ |
| P2X receptors | ATP Adenosine triphosphate Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism... |
Ca2+, Na+, Mg2+ |
Intracellular ligands
| Receptor | Ligand | Ion current |
| cyclic nucleotide-gated ion channel Cyclic nucleotide-gated ion channel Cyclic nucleotide-gated ion channels are ion channels that function in response to the binding of cyclic nucleotides. CNG channels are nonselective cation channels that are found in the membranes of various types of cells.- Discovery :... s |
cGMP Cyclic guanosine monophosphate Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP... (vision Visual system The visual system is the part of the central nervous system which enables organisms to process visual detail, as well as enabling several non-image forming photoresponse functions. It interprets information from visible light to build a representation of the surrounding world... ), cAMP Cyclic adenosine monophosphate Cyclic adenosine monophosphate is a second messenger important in many biological processes... and cGTP (olfaction) |
Na+, K+ |
| IP3 receptor Inositol triphosphate receptor Inositol trisphosphate receptor is a membrane glycoprotein complex acting as Ca2+ channel activated by inositol trisphosphate . InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis,... |
IP3 Inositol triphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate , together with diacylglycerol , is a secondary messenger molecule used in signal transduction and lipid signaling in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell... |
Ca2+ |
| Intracellular ATP Adenosine triphosphate Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism... receptors |
ATP Adenosine triphosphate Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism... (closes channel) |
K+ |
| Ryanodine receptor Ryanodine receptor Ryanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons... |
Ca2+ | Ca2+ |
The entire repertoire of human plasma membrane receptors is listed at the Human Plasma Membrane Receptome (http://www.receptome.org).
Various
- Ionotropic receptors (IP3 receptorInositol triphosphate receptorInositol trisphosphate receptor is a membrane glycoprotein complex acting as Ca2+ channel activated by inositol trisphosphate . InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis,...
above) - sigma1Sigma-1 receptorThe sigma-1 receptor is a chaperone protein at the endoplasmatic reticulum that modulates calcium signaling through the IP3 receptor. In humans, the sigma-1 receptor is encoded by the SIGMAR1 gene....
(neurosteroidsNeuroactive steroidNeuroactive steroids rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. In addition, these steroids may also exert effects on gene expression via intracellular steroid hormone receptors...
) - G protein-coupled receptors
Role in genetic disorders
Many genetic disorderGenetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s involve hereditary defects in receptor genes. Often, it is hard to determine whether the receptor is nonfunctional or the hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
is produced at decreased level; this gives rise to the "pseudo-hypo-" group of endocrine disorders
Endocrinology
Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation and the coordination of...
, where there appears to be a decreased hormonal level while in fact it is the receptor that is not responding sufficiently to the hormone.
Receptor regulation
Cells can increase (upregulate) or decrease (downregulate) the number of receptors to a given hormoneHormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
or neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
to alter its sensitivity to this molecule. This is a locally acting feedback
Feedback
Feedback describes the situation when output from an event or phenomenon in the past will influence an occurrence or occurrences of the same Feedback describes the situation when output from (or information about the result of) an event or phenomenon in the past will influence an occurrence or...
mechanism.
Receptor desensitization
- Uncoupling of receptor effector molecules.
- Receptor sequestrationEndocytosisEndocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
(internalization).
In immune system
The main receptors in the immune systemImmune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
are pattern recognition receptors (PRRs), toll-like receptor
Toll-like receptor
Toll-like receptors are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes...
s (TLRs), killer activated and killer inhibitor receptors (KARs and KIRs), complement receptor
Complement receptor
A complement receptor is a receptor of the complement system, a part of the mediated innate immune system. Complement receptors are responsible for detecting pathogens by mechanisms not mediated by antibodies. Complement activity is not antigen sensitive, but can be triggered by specific antigens...
s, Fc receptors, B cell receptors and T cell receptor
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
s.
See also
- Ki DatabaseKi DatabaseThe Ki Database is a public domain database of published binding affinities of drugs and chemical compounds for receptors, neurotransmitter transporters, ion channels, and enzymes...
- Ion channel linked receptorsIon channel linked receptorsIon channel linked receptors are cell membrane bound receptors. They act through synaptic signaling on electrically excitable cells. The ion channels opening and closing is controlled by neurotransmitters....
- NeuropsychopharmacologyNeuropsychopharmacologyNeuropsychopharmacology is an interdisciplinary science related to psychopharmacology and fundamental neuroscience...
- Schild regressionSchild regressionSchild regression analysis, named for Heinz Otto Schild, is a useful tool for studying the effects of agonists and antagonists on the cellular response caused by the receptor or on ligand-receptor binding....
for ligand receptor inhibition - Signal transductionSignal transductionSignal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
- Stem cell markerStem cell markerStem cell markers are genes and their protein products used by scientists to isolate and identify stem cells. Stem cells can also be identified by functional assays. Below is a list of genes/protein products that can be used to identify various types of stem cells, or functional assays that do the...
- Wikipedia:MeSH D12.776#MeSH D12.776.543.750 – receptors.2C cell surface