Muscarinic receptors, or
mAChRs, are
G protein-coupledG protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
acetylcholine receptorAn acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...
s found in the plasma membranes of certain neurons and other
cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
s. They play several roles, including acting as the main end-receptor stimulated by
acetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans. Acetylcholine is one of many neurotransmitters in the autonomic nervous system and the only neurotransmitter used in the motor division...
released from
postganglionic fibersIn the autonomic nervous system, fibers from the ganglion to the effector organ are called postganglionic fibers.-Neurotransmitters:The neurotransmitters used for postganglionic fibers differ:...
in the
parasympathetic nervous systemThe parasympathetic nervous system is a division of the autonomic nervous system , along with the sympathetic nervous system and enteric nervous system . The ANS is a subdivision of the peripheral nervous system . ANS sends fibers to three tissues: cardiac muscle, smooth muscle, or glandular tissue...
.
Muscarinic receptors were named as such because they are more sensitive to
muscarineMuscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. It was first isolated from Amanita muscaria in 1869...
than to
nicotineNicotine is an alkaloid found in the nightshade family of plants which constitutes approximately 0.6–3.0% of dry weight of tobacco, with biosynthesis taking place in the roots, and accumulating in the leaves...
. Their counterparts are
nicotinic acetylcholine receptorNicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons...
s (nAChRs), receptor ion channels that are also important in the
autonomic nervous systemThe autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
. Many drugs and other substances (for example
pilocarpinePilocarpine is a muscarinic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its topical...
and
scopolamineScopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is obtained from plants of the family Solanaceae , such as henbane, jimson weed and Angel's Trumpets , and corkwood . It is among the secondary metabolites of these plants...
) manipulate these two distinct receptors by acting as selective
agonistAn agonist is a drug that binds to a receptor of a cell and triggers a response by the cell. An agonist often mimics the action of a naturally occurring substance.An agonist produces an action...
s or
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...
s.
Pharmacological application
LigandsIn biochemistry and pharmacology, a ligand is a substance that is able to bind to and form 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...
targeting the mAChR that are currently approved for clinical use include non-selective antagonists for the treatment of
Parkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills, speech, and other functions....
,
atropineAtropine is a tropane alkaloid extracted from deadly nightshade , jimsonweed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. It is a competitive antagonist for the muscarinic acetylcholine...
(to dilate the
pupilThe pupil is an opening located in the center of the iris of the eye that allows light to enter the retina. It appears black because most of the light entering the pupil is absorbed by the tissues inside the eye. In humans the pupil is round, but other species, such as some cats, have slit pupils...
),
ScopolamineScopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is obtained from plants of the family Solanaceae , such as henbane, jimson weed and Angel's Trumpets , and corkwood . It is among the secondary metabolites of these plants...
(used to prevent
motion sicknessMotion sickness or kinetosis, also known as Travel Sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...
), and
ipratropiumIpratropium is an anticholinergic drug.-Uses:It is administered by inhalation for the treatment of obstructive lung diseases....
(used in the treatment of
asthmaAsthma is a predisposition to chronic inflammation of the lungs in which the airways are reversibly narrowed. Asthma affects 7% of the population of the United States, and 300 million worldwide...
).
Function
Acetylcholine (ACh) is a
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
found extensively in the
brainThe brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all...
and autonomic nervous system. It is also the neurotransmitter used to cause voluntary muscle contraction. Muscarinic receptors are used in the following roles:
Recovery receptors
ACh is always used as the transmitter within the
autonomic ganglionAutonomic ganglia are clusters of neuronal cell bodies and their dendrites and are essentially a junction between autonomic nerves originating from the central nervous system and autonomic nerves innervating their target organs in the periphery....
. Nicotinic receptors on the postganglionic neuron are responsible for the initial fast depolarization (Fast EPSP) of that neuron. As a consequence of this, nicotinic receptors are often cited as
the receptor on the postganglionic neurons at the ganglion. However, the subsequent hyperpolarization (IPSP) and slow depolarization (Slow EPSP) which represent the recovery of the postganglionic neuron from stimulation are actually mediated by
muscarinic receptors, types M
2 and M
1 respectively (discussed below). Peripheral autonomic fibers (sympathetic and parasympathetic fibers) are categorized anatomically as either preganglionic or postganglionic fibers then further generalized as either adrenergic fibers with their corresponding adrenergic receptors or cholinergic fibers with their cholinergic receptors. Both preganglionic sympathetic fibers and preganglionic parasympathetic fibers are cholinergic. All postganglionic sympathetic fibers are adrenergic, the neurotransmitter being norepinephrine, except for the postganglionic sympathetic fibers to the sweat glands, piloerectile muscles of the body hairs and the skeletal muscle arterioles. The adrenal medulla is considered a sympathetic ganglion and like other sympathetic ganglia it is supplied by cholinergic preganglionic sympathetic fibers, acetylcholine being the neurotransmitter. The other postganglionic fibers of the peripheral autonomic system belong to the parasympathetic division and all are cholinergic fibers, the neurotransmitter being acetylcholine (ACh). ACh has two types of effects. The first type is termed muscarinic, which is the parasympathetic effect on the secretory exocrine gland and smooth and cardiac muscles upon their corresponding receptors. The other type of ACh effect is termed nicotinic, which is on the skeletal (voluntary) muscles and not considered to be part of the peripheral autonomic nervous system.
Postganglionic neurons
Another role for these receptors is at the junction of the innervated tissue and the postganglionic neuron in the parasympathetic division of the autonomous nervous system. Here acetylcholine is again used as a neurotransmitter, and
muscarinic receptors form the principal receptors on the innervated tissue. In addition, muscarinic acetylcholine receptors pre-synaptically on the post-ganglionic neuron bind to the released acetylcholine and regulate the response of the postganglionic neuron.
Innervated tissue
By contrast, this junction in the sympathetic division mostly does not use acetylcholine as a neurotransmitter; instead, norepinephrine is used. Therefore neither muscarinic nor nicotinic receptors are involved, but
adrenergicThe adrenergic receptors are a class of G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
α1The alpha-1 adrenergic receptor is an adrenergic receptor with the primary effect of vasoconstriction.-Effect:The α1 receptor has several, general, functions in common with other α-receptors, but also has specific effects....
and
β1The beta-1 adrenergic receptor , also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it.-Actions:Actions of the β1 receptor include:...
receptors. Very few parts of the sympathetic system use cholinergic receptors (some postganglionic fibers terminating on sweat glands, which release acetylcholine, and in the kidney, which release dopamine are of the few exceptions). In sweat glands the receptors are of the
muscarinic type. The sympathetic nervous system also has some preganglionic nerves terminating at the
chromaffin cellChromaffin cells are neuroendocrine cells found in the medulla of the adrenal gland and in other ganglia of the sympathetic nervous system. They are derived from the embryonic neural crest....
s in the
adrenal medullaThe adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex.-Basic:The adrenal medulla consists of irregularly shaped cells grouped around blood vessels. These cells are intimately connected with the sympathetic division of the...
, which secrete
epinephrineEpinephrine is a hormone and neurotransmitter that participates in the "fight or flight" response of the sympathetic nervous system...
and
norepinephrineNoradrenaline or norepinephrine is a catecholamine with dual roles as a hormone and a neurotransmitter....
into the bloodstream. Some believe that chromaffin cells are modified postganglionic SNS fibers. In the adrenal medulla acetylcholine is used as a neurotransmitter, and the receptor is of the
nicotinic type. The somatic nervous system uses acetylcholine at the junction between its one peripheral nerve and the innervated tissue, also of the nicotinic type.
Higher central nervous system
Muscarinic acetylcholine receptors are also present and distributed throughout the central nervous system, in post-synaptic and pre-synaptic positions. There is also some evidence for postsynaptic receptors on sympathetic neurons allowing the parasympathetic nervous system to inhibit sympathetic effects.
Presynaptic membrane of the neuromuscular junction
It's now known they also appear on the pre-synaptic membrane of somatic neurons in the neuro-muscular junction, where they are involved in the regulation of acetylcholine release.
Form of muscarinic receptors
Muscarinic acetylcholine receptors belong to a class of
metabotropic 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 which use
G proteinG proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades.G proteins are so called because they function as "molecular switches," alternating between an inactive guanosine diphosphate and active guanosine triphosphate bound state,...
s as their signalling mechanism. There are known to be a large number of these G-protein-coupled receptors for
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
s,
hormoneA hormone is a chemical released by one or more cells that affects cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. It is essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms...
s, and other substances. G proteins are also present in taste, and odour detecting
cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
s, in the
retinaThe vertebrate retina is a light sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
, and in many other systems.
In such receptors, the signalling molecule (the
ligandIn chemistry, a ligand is either an atom, ion, or molecule that binds to a central metal-atom to produce a coordination complex. The bonding between the metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The metal-ligand bonding ranges from covalent...
) binds to a
receptorIn biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach...
which has seven transmembrane regions, in this case the ligand is ACh. This receptor is bound to intracellular proteins, known as G proteins, which begin the information cascade within the cell.
By contrast nicotinic receptors use an
ion-gatedLigand-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...
mechanism for signalling. Sufficient ligands cause an
ion channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
to open, filling (or evacuating) a cell of a particular ion.
Classification
By the use of selective radioactively-labelled agonist and antagonist substances, five subtypes of muscarinic receptors have been determined, named M
1-M
5 (using an upper case M and subscript number). For example, the drug
pirenzepinePirenzepine is used in the treatment of peptic ulcers, as it reduces gastric acid secretion and reduces muscle spasm...
is a muscarinic antagonist (decreases the effect of ACh) which is much more potent at M
1 receptors than it is at other subtypes. The acceptance of the various subtypes has proceeded in numerical order: therefore, sources exist which only recognise the M
1/M
2 distinction, more recent studies tend to recognise M
3, and the most recent M
4.
Genetic differences
Meanwhile,
geneticistA geneticist is a scientist who studies genetics, the science of heredity and variation of organisms. A geneticist can be employed as a researcher or lecturer...
s and molecular biologists have characterised five genes which appear to encode muscarinic receptors, named m1-m5 (lower case m; no subscript number). The first four code for pharmacologic types M
1-M
4. The fifth, M5, corresponds to a subtype of receptor which has not been detected pharmacologically. M1 and M2 were determined based upon partial sequencing of M
1 and M
2 receptor proteins, the others were found by searching for homology, using bioinformatic techniques.
Difference in G proteins
G proteins contain an alpha-subunit which is critical to the functioning of receptors. These subunits can take a number of forms. There are four broad classes of form of G-protein, G
s, G
i, G
q and G
12/13. Muscarinic receptors vary in the G protein to which they are bound, with some correlation according to receptor type. G proteins are also classified according to their susceptibility to
cholera toxinCholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the harmful effects of cholera infection.- Structure :...
(CTX) and
pertussis toxinPertussis toxin is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis, which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection...
(PTX, whooping cough). G
s and some subtypes of G
i (G
αt and G
αg) are susceptible to CTX. Only G
i is susceptible to PTX, with the exception of one subtype of G
i (G
αz) which is immune. Also, only when bound with an agonist, those G proteins normally sensitive to PTX also become susceptible to CTX.
The various G-protein subunits act differently upon secondary messengers, upregulating Phospholipases, downregulating cAMP, and so on.
Because of the strong correlations to muscarinic receptor type, CTX and PTX are useful experimental tools in investigating these receptors.
Comparison of types
| Type |
Gene |
Function |
PTX Pertussis toxin is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis, which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection...
|
CTX Cholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the harmful effects of cholera infection.- Structure :...
|
Effectors |
Agonists |
|
>-
| M1The muscarinic acetylcholine receptor M1, also known as the cholinergic receptor, muscarinic 1, is a muscarinic receptor.This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve, is common in exocrine glands and in the CNS.It is predominantly found bound to...
|
- EPSP
In neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels...
in autonomic ganglia
- secretion from salivary gland
The salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into glucose...
s and stomachIn most mammals, the stomach is a hollow, muscular organ of the gastrointestinal tract , between the esophagus and the small intestine. It is involved in the second phase of digestion, following mastication . The word stomach is derived from the Latin stomachus, which derives from the Greek word...
- In CNS
The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
(memory?) |
no
(yes) |
no
(yes) |
Gq Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate...
(GiGi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :...
)
(GsThe Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP dependent pathway by activating adenylate cyclase. Researchers have discovered that a change in the location of this protein in the brain could serve as a biomarker for depression, allowing a simple,...
):
Slow EPSP.
↓ K+Potassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
conductance |
acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans. Acetylcholine is one of many neurotransmitters in the autonomic nervous system and the only neurotransmitter used in the motor division...
oxotremorineOxotremorine is a synthetic alkaloid and is a muscarinic agonist in that it will bind to muscarinic acetylcholine receptors. It is therefore a parasympathomimetic.Specifically, oxotremorine is a non-selective muscarinic receptor agonist....
muscarineMuscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. It was first isolated from Amanita muscaria in 1869...
carbacholCarbachol, also known as carbamylcholine , is a drug that binds and activates the acetylcholine receptor. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery...
McNA343
|
atropineAtropine is a tropane alkaloid extracted from deadly nightshade , jimsonweed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. It is a competitive antagonist for the muscarinic acetylcholine...
scopolamineScopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is obtained from plants of the family Solanaceae , such as henbane, jimson weed and Angel's Trumpets , and corkwood . It is among the secondary metabolites of these plants...
dicycloverine
tolterodineTolterodine is an antimuscarinic drug that is used to treat urinary incontinence. It is sold under the trade names Detrol and Detrusitol.-Pharmacology:...
oxybutyninOxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination , by decreasing muscle spasms of the bladder. It competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine receptor...
ipratropiumIpratropium is an anticholinergic drug.-Uses:It is administered by inhalation for the treatment of obstructive lung diseases....
mamba toxin MT7
pirenzepinePirenzepine is used in the treatment of peptic ulcers, as it reduces gastric acid secretion and reduces muscle spasm...
telenzepineTelenzepine is a parasympatholytic.-External links:...
>-
| M2The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor.-Function:...
|
|
- slow heart rate
Heart rate is determined by the number of heartbeats per unit of time, typically expressed as beats per minute , it can vary with as the body's need for oxygen changes, such as during exercise or sleep. The measurement of heart rate is used by medical professionals to assist in the diagnosis and...
- reduce contractile forces of atrium
- reduce conduction velocity of AV node
The atrioventricular node is a part of electrical control system of the heart that co-ordinates heart rate. It electrically connects atrial and ventricular chambers...
- In CNS
The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
- homotropic inhibition
|
yes |
no |
Gi Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :...
↑ K+Potassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
conductance
↓ Ca2+Calcium 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 grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
conductance |
acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans. Acetylcholine is one of many neurotransmitters in the autonomic nervous system and the only neurotransmitter used in the motor division...
methacholine
carbacholCarbachol, also known as carbamylcholine , is a drug that binds and activates the acetylcholine receptor. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery...
oxotremorineOxotremorine is a synthetic alkaloid and is a muscarinic agonist in that it will bind to muscarinic acetylcholine receptors. It is therefore a parasympathomimetic.Specifically, oxotremorine is a non-selective muscarinic receptor agonist....
muscarineMuscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. It was first isolated from Amanita muscaria in 1869...
|
atropineAtropine is a tropane alkaloid extracted from deadly nightshade , jimsonweed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. It is a competitive antagonist for the muscarinic acetylcholine...
dicycloverine
tolterodineTolterodine is an antimuscarinic drug that is used to treat urinary incontinence. It is sold under the trade names Detrol and Detrusitol.-Pharmacology:...
oxybutyninOxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination , by decreasing muscle spasms of the bladder. It competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine receptor...
ipratropiumIpratropium is an anticholinergic drug.-Uses:It is administered by inhalation for the treatment of obstructive lung diseases....
methoctramine
tripitamine
gallamineGallamine is a non-depolarising muscle relaxant also known under the trade name Flaxedil. It acts by combining with the cholinergic receptor sites in muscle and competitively blocking the transmitter action of acetylcholine. Gallamine has a parasympatholytic effect on the cardiac vagus nerve...
>-
| M3The muscarinic acetylcholine receptor M3, also known as the cholinergic receptor, muscarinic 3, is a muscarinic acetylcholine receptor. It is encoded by the human gene CHRM3....
|
|
- smooth muscle contraction
- increased endocrine and exocrine gland
Exocrine glands are glands that secrete their products into ducts . They are the counterparts to endocrine glands, which secrete their products directly into the bloodstream or release hormones that affect only target cells nearby the release site.-Examples:Typical exocrine glands include sweat...
secretions, e.g. salivary glands and stomachIn most mammals, the stomach is a hollow, muscular organ of the gastrointestinal tract , between the esophagus and the small intestine. It is involved in the second phase of digestion, following mastication . The word stomach is derived from the Latin stomachus, which derives from the Greek word...
- In CNS
The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
- Eye accommodation
Accommodation is the process by which the vertebrate :eye changes optical power to maintain a clear image on an object as its distance changes....
- vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
- induce emesis
|
no |
no |
Gq Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate...
|
acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans. Acetylcholine is one of many neurotransmitters in the autonomic nervous system and the only neurotransmitter used in the motor division...
bethanecholBethanechol is a parasympathomimetic choline ester that selectively stimulates muscarinic receptors without any effect on nicotinic receptors...
carbacholCarbachol, also known as carbamylcholine , is a drug that binds and activates the acetylcholine receptor. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery...
oxotremorineOxotremorine is a synthetic alkaloid and is a muscarinic agonist in that it will bind to muscarinic acetylcholine receptors. It is therefore a parasympathomimetic.Specifically, oxotremorine is a non-selective muscarinic receptor agonist....
pilocarpinePilocarpine is a muscarinic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its topical...
(in eye)
|
atropineAtropine is a tropane alkaloid extracted from deadly nightshade , jimsonweed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. It is a competitive antagonist for the muscarinic acetylcholine...
dicycloverine
tolterodineTolterodine is an antimuscarinic drug that is used to treat urinary incontinence. It is sold under the trade names Detrol and Detrusitol.-Pharmacology:...
oxybutyninOxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination , by decreasing muscle spasms of the bladder. It competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine receptor...
ipratropiumIpratropium is an anticholinergic drug.-Uses:It is administered by inhalation for the treatment of obstructive lung diseases....
darifenacinDarifenacin is a medication used to treat urinary incontinence.Darifenacin works by blocking the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions. It thereby decreases the urgency to urinate...
tiotropiumTiotropium is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease...
>-
| M4The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 , is a protein which in humans is encoded by the CHRM4 gene.-Function:...
|
|
- Enhanced locomotion
- In CNS
The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
|
yes |
? |
Gi Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :...
↑ K+Potassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
conductance
↓ Ca2+Calcium 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 grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
conductance |
acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans. Acetylcholine is one of many neurotransmitters in the autonomic nervous system and the only neurotransmitter used in the motor division...
carbacholCarbachol, also known as carbamylcholine , is a drug that binds and activates the acetylcholine receptor. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery...
oxotremorineOxotremorine is a synthetic alkaloid and is a muscarinic agonist in that it will bind to muscarinic acetylcholine receptors. It is therefore a parasympathomimetic.Specifically, oxotremorine is a non-selective muscarinic receptor agonist....
|
atropineAtropine is a tropane alkaloid extracted from deadly nightshade , jimsonweed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. It is a competitive antagonist for the muscarinic acetylcholine...
dicycloverine
tolterodineTolterodine is an antimuscarinic drug that is used to treat urinary incontinence. It is sold under the trade names Detrol and Detrusitol.-Pharmacology:...
oxybutyninOxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination , by decreasing muscle spasms of the bladder. It competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine receptor...
ipratropiumIpratropium is an anticholinergic drug.-Uses:It is administered by inhalation for the treatment of obstructive lung diseases....
mamba toxin MT3
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| M5The human muscarinic acetylcholine receptor M5 which is encoded by the gene is a member of the G protein-coupled receptor superfamily of integral membrane proteins...
CHRM5 |
- In CNS
The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
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no |
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Gq Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate...
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acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans. Acetylcholine is one of many neurotransmitters in the autonomic nervous system and the only neurotransmitter used in the motor division...
carbacholCarbachol, also known as carbamylcholine , is a drug that binds and activates the acetylcholine receptor. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery...
oxotremorineOxotremorine is a synthetic alkaloid and is a muscarinic agonist in that it will bind to muscarinic acetylcholine receptors. It is therefore a parasympathomimetic.Specifically, oxotremorine is a non-selective muscarinic receptor agonist....
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- atropine
Atropine is a tropane alkaloid extracted from deadly nightshade , jimsonweed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. It is a competitive antagonist for the muscarinic acetylcholine...
- dicycloverine
- tolterodine
Tolterodine is an antimuscarinic drug that is used to treat urinary incontinence. It is sold under the trade names Detrol and Detrusitol.-Pharmacology:...
- oxybutynin
Oxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination , by decreasing muscle spasms of the bladder. It competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine receptor...
- ipratropium
Ipratropium is an anticholinergic drug.-Uses:It is administered by inhalation for the treatment of obstructive lung diseases....
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M1 receptor
This receptor is found mediating slow
EPSPIn neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels...
at the ganglion in the postganglionic nerve, is common in
exocrine glandExocrine glands are glands that secrete their products into ducts . They are the counterparts to endocrine glands, which secrete their products directly into the bloodstream or release hormones that affect only target cells nearby the release site.-Examples:Typical exocrine glands include sweat...
s and in the CNS.
It is predominantly found bound to G proteins of class
GqGq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate...
which use upregulation of
phospholipaseA phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D distinguished by what type of reaction they catalyze:* Phospholipase A...
C and therefore inositol trisphosphate and intracellular calcium as a signalling pathway. A receptor so bound would not be susceptible to CTX or PTX. However, G
i (causing a downstream decrease in
cAMPCyclic adenosine monophosphate is a second messenger important in many biological processes...
) and G
s (causing an increase in cAMP) have also been shown to be involved in interactions in certain tissues, and so would be susceptible to PTX and CTX respectively.
M2 receptor
The M
2 muscarinic receptors are located in the heart, where they act to slow the
heart rateHeart rate is determined by the number of heartbeats per unit of time, typically expressed as beats per minute , it can vary with as the body's need for oxygen changes, such as during exercise or sleep. The measurement of heart rate is used by medical professionals to assist in the diagnosis and...
down to normal
sinus rhythmSinus rhythm is a term used in medicine to describe the normal beating of the heart, as measured by an electrocardiogram . It has certain generic features that serve as hallmarks for comparison with normal ECGs.- ECG Structure :...
after stimulatory actions of the sympathetic nervous system, by slowing the speed of
depolarizationIn biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
. They also reduce contractile forces of the atrial
cardiac muscleCardiac muscle is a type of involuntary striated muscle found in the walls of the heart, specifically the myocardium. Cardiac muscle cells are known as cardiac myocytes . Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
, and reduce conduction velocity of the
atrioventricular nodeThe atrioventricular node is a part of electrical control system of the heart that co-ordinates heart rate. It electrically connects atrial and ventricular chambers...
(AV node). It also serves to slightly decrease the contractile forces of the ventricular muscle.
M
2 muscarinic receptors act via a
GiGi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :...
type receptor, which causes a decrease in cAMP in the cell, generally leading to inhibitory-type effects.
Effects include formation of IP3 and DAG/
M3 receptor
The M
3 muscarinic receptors are located at many places in the body. They are located in the smooth muscles of the blood vessels, as well as in the lungs. Because the M
3 receptor is G
q-coupled and mediates an increase in intracellular calcium, it typically causes constriction of smooth muscle, such as that observed during
bronchoconstrictionBronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Bronchoconstriction can also be due to an accumulation of thick mucus.-Causes:...
. However, with respect to vasculature, activation of M
3 on vascular endothelial cells causes increased synthesis of nitric oxide which diffuses to adjacent vascular smooth muscle cells and causes their relaxation thereby explaining the paradoxical effect of parasympathomimetics on vascular tone and bronchiolar tone. Indeed, direct stimulation of vascular smooth muscle M
3 mediates vasconstriction in pathologies whereby the vascular endothelium is disrupted.
The M
3 receptors are also located in many glands which help to stimulate secretion in salivary glands and other glands of the body.
Like the M
1 muscarinic receptor, M
3 receptors are G proteins of class
GqGq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate...
which upregulate phospholipase C and therefore inositol trisphosphate and intracellular calcium as a signalling pathway.
M4 receptor
M
4 receptors are found in the CNS.
Receptors work via
GiGi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :...
receptors to decrease cAMP in the cell and thus produce generally inhibitory effects.
M5 receptor
Location of M
5 receptors is not well known.
Like the M
1 and M
3 muscarinic receptor, M
5 receptors are coupled with G proteins of class
GqGq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate...
which upregulate phospholipase C and therefore inositol trisphosphate and intracellular calcium as a signalling pathway.
See also
- Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons...
- Muscarinic receptor agonist
A muscarinic receptor agonist is an agent that enhances the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, labelled M1-M5, allowing for further differentiation.- M1 :...
- Tiotropium
Tiotropium is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease...