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Gastrin
 
 
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In humans, gastrin is a hormone
Hormone

Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism....
 that stimulates secretion of gastric acid
Gastric acid

Gastric acid is one of the main secretions of the stomach, together with several enzymes and intrinsic factor. Chemically it is an acid solution with a pH of 1 to 2 in the stomach lumen , consisting mainly of hydrochloric acid , and large quantities of potassium chloride and sodium chloride ....
 (HCl) by the parietal cell
Parietal cell

Parietal cells, or oxyntic cells, are the stomach epithelium cell s that secrete gastric acid and intrinsic factor....
s of the stomach
Stomach

In most mammals, the stomach is a hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication....
 and aids in gastric motility. It is released by G cell
G cell

In anatomy, the G cell is a type of cell in the stomach that secretes gastrin. It works in conjunction with gastric chief cells and parietal cells....
s in the stomach, duodenum
Duodenum

The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum....
, and the pancreas
Pancreas

The pancreas is a gland Organ in the digestive system and endocrine system of vertebrates. It is both an endocrine gland , as well as an exocrine gland, secreting pancreatic juice containing Digestion enzymes that pass to the small intestine....
. Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins, and gastrins were isolated in 1964 by Gregory and Tracy in Liverpool
Liverpool

Liverpool [] is a city and metropolitan borough of Merseyside, England, along the eastern side of the Mersey Estuary. It was founded as a History of borough status in England and Wales in 1207 and was granted City status in the United Kingdom in 1880....
.

GAS gene is located on the long arm of the seventeenth chromosome (17q21).

rin is a linear peptide hormone
Peptide hormone

Peptide hormones are a class of peptide that are secreted into the blood stream and have endocrine functions in living animals. Peptide hormones are increasingly being identified in plants with important roles in cell-to-cell communication and plant defence....
 produced by G cell
G cell

In anatomy, the G cell is a type of cell in the stomach that secretes gastrin. It works in conjunction with gastric chief cells and parietal cells....
s of the duodenum and in the pyloric antrum
Antrum

In Biology, "Antrum" is a general term for a cavity or chamber which may have specific meaning in reference to certain organs or sites in the body....
 of the stomach
Stomach

In most mammals, the stomach is a hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication....
.






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Control of Stomach Acid Sec
In humans, gastrin is a hormone
Hormone

Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism....
 that stimulates secretion of gastric acid
Gastric acid

Gastric acid is one of the main secretions of the stomach, together with several enzymes and intrinsic factor. Chemically it is an acid solution with a pH of 1 to 2 in the stomach lumen , consisting mainly of hydrochloric acid , and large quantities of potassium chloride and sodium chloride ....
 (HCl) by the parietal cell
Parietal cell

Parietal cells, or oxyntic cells, are the stomach epithelium cell s that secrete gastric acid and intrinsic factor....
s of the stomach
Stomach

In most mammals, the stomach is a hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication....
 and aids in gastric motility. It is released by G cell
G cell

In anatomy, the G cell is a type of cell in the stomach that secretes gastrin. It works in conjunction with gastric chief cells and parietal cells....
s in the stomach, duodenum
Duodenum

The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum....
, and the pancreas
Pancreas

The pancreas is a gland Organ in the digestive system and endocrine system of vertebrates. It is both an endocrine gland , as well as an exocrine gland, secreting pancreatic juice containing Digestion enzymes that pass to the small intestine....
. Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins, and gastrins were isolated in 1964 by Gregory and Tracy in Liverpool
Liverpool

Liverpool [] is a city and metropolitan borough of Merseyside, England, along the eastern side of the Mersey Estuary. It was founded as a History of borough status in England and Wales in 1207 and was granted City status in the United Kingdom in 1880....
.

Physiology


Genetics

The GAS gene is located on the long arm of the seventeenth chromosome (17q21).

Synthesis

Gastrin is a linear peptide hormone
Peptide hormone

Peptide hormones are a class of peptide that are secreted into the blood stream and have endocrine functions in living animals. Peptide hormones are increasingly being identified in plants with important roles in cell-to-cell communication and plant defence....
 produced by G cell
G cell

In anatomy, the G cell is a type of cell in the stomach that secretes gastrin. It works in conjunction with gastric chief cells and parietal cells....
s of the duodenum and in the pyloric antrum
Antrum

In Biology, "Antrum" is a general term for a cavity or chamber which may have specific meaning in reference to certain organs or sites in the body....
 of the stomach
Stomach

In most mammals, the stomach is a hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication....
. It is secreted into the bloodstream. Gastrin is found primarily in three forms:
  • gastrin-34 ("big gastrin")
  • gastrin-17 ("little gastrin")
  • gastrin-14 ("minigastrin")


Also, pentagastrin
Pentagastrin

Pentagastrin is a synthetic polypeptide that has effects like gastrin when given parenterally. It stimulates the secretion of gastric acid, pepsin, and intrinsic factor, and has been used as a diagnosis aid as the pentagastrin-stimulated calcitonin test....
 is an artificially synthesized, five amino acid sequence identical to the last five amino acid sequence at the C-terminus end of gastrin.

The numbers refer to the amino acid
Amino acid

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent....
 count.

Release

Gastrin is released in response to certain stimuli. These include:
  • stomach distension
    Distension

    Distension generally refers to an enlargement or ballooning effect:* Gastric distension - bloating of the stomach when air is pumped into it, as in a medical procedure...
  • vagal
    Vagus nerve

    The vagus nerve is the tenth of twelve paired cranial nerves, and is the only nerve that starts in the brainstem and extends, through the jugular foramen, down below the head , to the neck, chest and abdomen, where it contributes to the innervation of the viscera....
     stimulation (mediated by the neurocrine
    Neurocrine

    Neurocrine can refer to:* A type of cell signaling similar to paracrine, but involving neurons. See chemical synapse for more details.* Neurocrine Biosciences...
     bombesin
    Bombesin

    Bombesin is a 14 amino acid peptide originally isolated from the skin of a frog. It has two known homologs in mammals called neuromedin B and gastrin releasing peptide....
    , or GRP
    Gastrin releasing peptide

    Gastrin-releasing peptide, also known as GRP, is an important regulatory molecule which has been implicated in a number of physiological and pathophysiological processes in the human organism....
     in humans)
  • the presence of partially digested
    Digestion

    Digestion is the mechanical and chemical breaking down of food into smaller components, to a form that can be Absorption, for instance, by a blood stream....
     protein
    Protein

    Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
    s especially amino acids
  • hypercalcemia


Gastrin release is inhibited by:
  • The presence of acid
    Acid

    An acid is traditionally considered any chemical compound that, when dissolved in water, gives a solution with a hydrogen ion Activity greater than in pure water, i.e....
     (primarily the secreted HCl) in the stomach (a case of negative feedback
    Negative feedback

    Negative feedback feeds part of a system's output, inverted, into the system's input; generally with the result that fluctuations are attenuated....
    ).
  • Somatostatin
    Somatostatin

    Somatostatin 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....
     also inhibits the release of gastrin, along with secretin
    Secretin

    Secretin is a peptide hormone produced in the S cells of the duodenum in the crypts of Lieberk?hn. Its primary effect is to regulate the pH of the duodenal contents via the control of gastric acid secretion and buffering with bicarbonate....
    , GIP (gastroinhibitory peptide
    Gastroinhibitory peptide

    Gastroinhibitory polypeptides or Gastroinhibitory peptides , are physiologically important in potentiating insulin release. GIP stimulates insulin release when glucose concentration is elevated....
    ), VIP, glucagon
    Glucagon

    Glucagon is an important hormone involved in carbohydrate metabolism. Produced by the pancreas, it is released when the glucose level in the blood is low , causing the liver to convert stored glycogen into glucose and release it into the bloodstream....
     and calcitonin
    Calcitonin

    Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the Parafollicular cell cells of the thyroid, and in many other animals in the ultimobranchial body....
    .


Function

The presence of gastrin stimulates parietal cell
Parietal cell

Parietal cells, or oxyntic cells, are the stomach epithelium cell s that secrete gastric acid and intrinsic factor....
s of the stomach to secrete hydrochloric acid
Hydrochloric acid

Hydrochloric acid is the solution of hydrogen chloride in water. It is a highly corrosive, strong acid mineral acid and has major industrial uses....
 (HCl)/gastric acid. This is done indirectly via binding onto CCK2/gastrin receptors
Cholecystokinin B receptor

The Cholecystokinin B receptor is a human protein that is also known as CCKBR or CCK2, with CCK2 now being the IUPHAR-recommended name....
 on ECL cells in the stomach, which then responds by releasing histamine
Histamine

Histamine is a biogenic amine involved in local immune system as well as regulating physiological function in the gut and acting as a neurotransmitter....
, which in turn acts in a paracrine manner on parietal cells stimulating them to secrete H+ ions. This is the major stimulus for acid secretion by parietal cells.

Direct binding of gastrin to the parietal cells is involved in parietal cell maturation and fundal growth.

Gastrin also causes chief cells
Gastric chief cell

A gastric chief cell is a cell in the stomach that releases pepsinogen, gastric lipase and rennin. The cell stains basophilic upon H&E stain due to the large proportion of rough endoplasmic reticulum in its cytoplasm....
 to secrete pepsinogen, the zymogen
Zymogen

A zymogen is an inactive enzyme Protein precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it....
 (inactive) form of the digestive enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 pepsin
Pepsin

Pepsin is an enzyme that is released by the gastric chief cells in the stomach and which degrades food proteins into peptides. Pepsin was discovered in 1836 by Theodor Schwann who also coined this enzyme's name from the Greek language word pepsis, meaning digestion ....
. Pepsinogen is converted to pepsin in a low pH
PH

pH is a measure of the Acid or Base of a solution. It is defined as the cologarithm of the Activity of dissolved hydrogen ions . Hydrogen ion activity coefficients cannot be measured experimentally, so they are based on theoretical calculations....
 environment, and the HCl provides a suitable environment for its activity. It can also increase antral muscle mobility and trophic effect on GI tract and causes promotion of contraction of circular muscle of the stomach. In digestion, gastrin strengthens the antral contractions against the pylorus, and constricts the pyloric sphincter, which has the effect of slowing the rate of gastric emptying.

Gastrin has also been shown to induce production of pancreatic
Pancreas

The pancreas is a gland Organ in the digestive system and endocrine system of vertebrates. It is both an endocrine gland , as well as an exocrine gland, secreting pancreatic juice containing Digestion enzymes that pass to the small intestine....
 enzymes by centroacinar cells
Centroacinar cells

In some animals spindle-shaped cells occupy the center of the alveolus of the pancreas and are known as the centroacinar cells of Langerhans. These cells are commonly known as Duct , and secrete an aqueous bicarbonate solution under stimulation by the hormone secretin....
. It increases gastric blood flow.

Factors influencing secretion

Gastric lumen:
  • Stimulatory factors: dietary protein and amino acids, hypercalcemia. (i.e. during the gastric phase)
  • Inhibitory factor: acidity (pH below 3) - a negative feedback mechanism, exerted via the release of somatostatin from d cell
    Delta cell

    Delta cells are somatostatin producing cell s.They can be found in the stomach, intestine and the Islets of Langerhans in the pancreas.In rodents delta-cells are located in the periphery of the islets; in humans the islet architecture is generally less organized and delta-cells are frequently observed inside the islets as well....
    s in the stomach, which inhibits gastrin and histamine release.


Paracrine:
  • Stimulatory factor: bombesin
    Bombesin

    Bombesin is a 14 amino acid peptide originally isolated from the skin of a frog. It has two known homologs in mammals called neuromedin B and gastrin releasing peptide....
  • Inhibitory factor: somatostatin
    Somatostatin

    Somatostatin 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....
     - acts on somatostatin-2 receptors on G cells. in a paracrine manner via local diffusion in the intercellular spaces, but also systemically through its release into the local mucosal blood circulation; it inhibits acid secretion by acting on parietal cells.


Nervous:
  • Stimulatory factors: Beta-adrenergic agents, cholinergic
    Cholinergic

    A receptor is cholinergic if it uses acetylcholine as its neurotransmitter.Cholinergic means related to the neurotransmitter acetylcholine, and is typically used in a neurological perspective....
     agents, gastrin-releasing peptide (GRP)
Circulation:
  • Stimulatory factor: epinephrine
    Epinephrine

    Epinephrine is a hormone and neurotransmitter.Epinephrine increases the "fight or flight" response of the Sympathetic nervous system of the autonomic nervous system....
  • Inhibitory factors:gastric inhibitory peptide (GIP), secretin
    Secretin

    Secretin is a peptide hormone produced in the S cells of the duodenum in the crypts of Lieberk?hn. Its primary effect is to regulate the pH of the duodenal contents via the control of gastric acid secretion and buffering with bicarbonate....
    , somatostatin
    Somatostatin

    Somatostatin 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....
    , glucagon
    Glucagon

    Glucagon is an important hormone involved in carbohydrate metabolism. Produced by the pancreas, it is released when the glucose level in the blood is low , causing the liver to convert stored glycogen into glucose and release it into the bloodstream....
    , calcitonin
    Calcitonin

    Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the Parafollicular cell cells of the thyroid, and in many other animals in the ultimobranchial body....


Role in disease

In the Zollinger-Ellison syndrome
Zollinger-Ellison syndrome

Zollinger-Ellison syndrome is a disorder where increased levels of the hormone gastrin are produced, causing the stomach to produce excess hydrochloric acid....
, gastrin is produced at excessive levels, often by a gastrinoma
Gastrinoma

A gastrinoma is a tumor that secretes gastrin.It is frequently the source of the gastrin in Zollinger-Ellison syndrome.It is most commonly found in the duodenum and less commonly in the pancreas....
 (gastrin-producing tumor, mostly benign) of the duodenum
Duodenum

The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum....
 or the pancreas
Pancreas

The pancreas is a gland Organ in the digestive system and endocrine system of vertebrates. It is both an endocrine gland , as well as an exocrine gland, secreting pancreatic juice containing Digestion enzymes that pass to the small intestine....
. To investigate for hypergastrinemia (high blood levels of gastrin), a "pentagastrin
Pentagastrin

Pentagastrin is a synthetic polypeptide that has effects like gastrin when given parenterally. It stimulates the secretion of gastric acid, pepsin, and intrinsic factor, and has been used as a diagnosis aid as the pentagastrin-stimulated calcitonin test....
 test" can be performed.

In autoimmune gastritis
Gastritis

Gastritis is an inflammation of the lining of the stomach, and has many possible causes. The main acute causes are excessive alcohol consumption or prolonged use of nonsteroidal anti-inflammatory drugs such as aspirin or ibuprofen....
, the immune system attacks the parietal cells leading to hypochlorhydria (low stomach acidity). This results in an elevated gastrin level in an attempt to compensate for low acidity. Eventually, all the parietal cells are lost and achlorhydria
Achlorhydria

Achlorhydria and hypochlorhydria refer to states where the production of gastric acid in the stomach is absent or low, respectively. It is associated with various other medical problems....
 results leading to a loss of negative feedback
Negative feedback

Negative feedback feeds part of a system's output, inverted, into the system's input; generally with the result that fluctuations are attenuated....
 on gastrin secretion.

Further reading


External links