Gastrin
Encyclopedia
Peptide hormone
Peptide 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...
that stimulates secretion of gastric acid
Gastric acid
Gastric acid is a digestive fluid, formed in the stomach. It has a pH of 1 to 2 and is composed of hydrochloric acid , and large quantities of potassium chloride and sodium chloride...
(HCl) by the parietal cells of the stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
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.G cells are found deep within the gastric glands of the stomach antrum, and occasionally in the pancreas....
s in the antrum of 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 and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
. It binds to cholecystokinin B receptor
Cholecystokinin B receptor
The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein that in humans is encoded by the CCKBR gene.This gene encodes a G protein-coupled receptor for gastrin and cholecystokinin , regulatory peptides of the brain and gastrointestinal tract...
s to stimulate the release of histamines in enterochromaffin-like cells, and it induces the insertion of K+/H+ Atpase pumps into the apical membrane of parietal cells (which in turn increases H+ release). Its release is stimulated by peptides in the lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
of the stomach.
History
Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins, and gastrins were isolated in 1964 by Roderic Alfred GregoryRoderic Alfred Gregory
Roderic Alfred Gregory CBE FRS was a British biologist.He was born in 1913 in Plaistow, London, the only child of Alfred Gregory and Alice Jane Gregory. His father was a fitter and turner who, in 1913, was employed by Brunner and Monde...
and Tracy at the University of Liverpool
University of Liverpool
The University of Liverpool is a teaching and research university in the city of Liverpool, England. It is a member of the Russell Group of large research-intensive universities and the N8 Group for research collaboration. Founded in 1881 , it is also one of the six original "red brick" civic...
. In 1964 the structure of Gastrin was determined.
Genetics
The GAS gene is located on the long arm of the seventeenth chromosome (17q21).Synthesis
Gastrin is a linear peptide hormonePeptide hormone
Peptide 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...
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.G cells are found deep within the gastric glands of the stomach antrum, and occasionally in the pancreas....
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.In vertebrates, it may mean for example:...
of the stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
. It is secreted into the bloodstream. Gastrin is found primarily in three forms:
- gastrin-34 ("big gastrinBig gastrinBig gastrin is a form of gastrin with 34 amino acids in the sequence....
") - gastrin-17 ("little gastrin")
- gastrin-14 ("minigastrinMinigastrinMinigastrin is a form of gastrin....
")
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 diagnostic aid as the pentagastrin-stimulated calcitonin test.Pentagastrin binds to the cholecystokinin-B...
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
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
count.
Release
Gastrin is released in response to certain stimuli. These include:- stomach distensionDistensionDistension 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* Abdominal distension - abdominal bloating, a symptom of several medical conditions...
- vagalVagus nerveThe vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
stimulation (mediated by the neurocrineNeurocrineNeurocrine can refer to:* A type of cell signaling similar to paracrine, but involving neurons. See chemical synapse for more details.* Neurocrine Biosciences...
bombesinBombesinBombesin 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. It stimulates gastrin release from G cells. It activates three different G-protein-coupled receptors known as BBR1, -2, and -3. It...
, or GRPGastrin releasing peptideGastrin-releasing peptide, also known as GRP, is an important regulatory molecule that has been implicated in a number of physiological and pathophysiological processes in humans....
in humans) - the presence of partially digestedDigestionDigestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....
proteinProteinProteins 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...
s especially amino acids - hypercalcemia
Gastrin release is inhibited by :
- The presence of acidAcidAn acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
(primarily the secreted HCl) in the stomach (a case of negative feedbackNegative feedbackNegative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
). - 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...
also inhibits the release of gastrin, along with 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...
, GIP (gastroinhibitory peptideGastroinhibitory peptideGastroinhibitory polypeptides or Gastroinhibitory peptides , are physiologically important in potentiating insulin release. GIP stimulates insulin release when glucose concentration is elevated....
), VIP (vasoactive intestinal peptideVasoactive intestinal peptideVasoactive intestinal peptide also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 29 amino acid residues that is produced in many tissues of vertebrates including the gut, pancreas and suprachiasmatic nuclei of the hypothalamus in the brain...
), 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...
and calcitoninCalcitoninCalcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...
.
Function
The presence of gastrin stimulates parietal cellParietal cell
Parietal cells, or oxyntic cells, are the stomach epithelium cells that secrete gastric acid and intrinsic factor.Acetylcholine and gastrin . The histamine receptors act by increasing intracellular cAMP, whereas the muscarinic and gastrin receptors increase intracellular Ca2+ levels...
s of the stomach to secrete hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
(HCl)/gastric acid. This is done both directly on the parietal cell and indirectly via binding onto CCK2/gastrin receptors
Cholecystokinin B receptor
The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein that in humans is encoded by the CCKBR gene.This gene encodes a G protein-coupled receptor for gastrin and cholecystokinin , regulatory peptides of the brain and gastrointestinal tract...
on ECL cells in the stomach, which then responds by releasing histamine
Histamine
Histamine 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...
, 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.
Along with the above mentioned function, gastrin has been shown to have additional functions as well:
- Stimulates parietal cell maturation and fundal growth.
- Causes chief cellsGastric chief cellA gastric chief cell is a cell in the stomach that releases pepsinogen, gastric lipase and Chymosin...
to secrete pepsinogen, the zymogenZymogenA zymogen is an inactive enzyme 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 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...
pepsinPepsinPepsin is an enzyme whose precursor form is released by the chief cells in the stomach and that degrades food proteins into peptides. It was discovered in 1836 by Theodor Schwann who also coined its name from the Greek word pepsis, meaning digestion...
. - Increases antral muscle mobility and promotes stomach contractions.
- Strengthens antral contractions against the pylorus, and relaxes the pyloric sphincter, which stimulates gastric emptying.
- Plays a role in the relaxation of the ileocecal valveIleocecal valveThe ileocecal valve, or ileocaecal valve, is of a bilabial papilla structure with physiological sphincter muscle situated at the junction of the small intestine and the large intestine, with recent evidence indicating an anatomical sphincter may also be present in humans) Its critical function is...
. - Induces pancreaticPancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
secretions and gallbladderGallbladderIn vertebrates the gallbladder is a small organ that aids mainly in fat digestion and concentrates bile produced by the liver. In humans the loss of the gallbladder is usually easily tolerated....
emptying. - Impacts lower esophageal sphincter (LES) tone, causing it to relax. Taking this into consideration, high levels of gastrin may play a role in the development of some of the more common LES disorders such as acid reflux disease.
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 δ cellDelta cellDelta cells are somatostatin-producing cells.They can be found in the stomach, intestine and the Islets of Langerhans in the pancreas....
s in the stomach, which inhibits gastrin and histamine release.
Paracrine:
- Stimulatory factor: bombesinBombesinBombesin 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. It stimulates gastrin release from G cells. It activates three different G-protein-coupled receptors known as BBR1, -2, and -3. It...
- Inhibitory factor: 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...
- 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, cholinergicCholinergicThe word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...
agents, gastrin-releasing peptide (GRP) - Inhibitory factor: Enterogastric reflexEnterogastric reflexThe Enterogastric reflex is one of three extrinsic reflexes of the Gastrointestinal Tract. The reflex is stimulated by the presence of acid levels in the duodenum at a pH of 3-4 or in the stomach at a pH of 1.5. Upon stimulation of the reflex, the release of gastrin from G-cells in the antrum of...
Circulation:
- Stimulatory factor: epinephrineEpinephrineEpinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
- Inhibitory factors:gastric inhibitory peptide (GIP), 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...
, 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...
, 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...
, calcitoninCalcitoninCalcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...
Role in disease
In the Zollinger-Ellison syndromeZollinger-Ellison syndrome
Zollinger–Ellison syndrome is a triad of gastric acid hypersecretion, severe peptic ulceration, and non-beta cell islet tumor of pancreas . In this syndrome increased levels of the hormone gastrin are produced, causing the stomach to produce excess hydrochloric acid. Often the cause is a tumor of...
, gastrin is produced at excessive levels, often by a gastrinoma
Gastrinoma
A gastrinoma is a tumor in the pancreas or duodenum that secretes excess of gastrin leading to ulceration in the duodenum, stomach and the small intestine. There is hypersecretion of the HCl in the duodenum which causes the ulcers...
(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 and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
. 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 diagnostic aid as the pentagastrin-stimulated calcitonin test.Pentagastrin binds to the cholecystokinin-B...
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. Sometimes gastritis develops after major surgery, traumatic...
, 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 increased pH in the stomach. Eventually, all the parietal cells are lost and achlorhydria
Achlorhydria
Achlorhydria or hypochlorhydria refers to states where the production of gastric acid in the stomach is absent or low, respectively. It is associated with various other medical problems.-Signs and symptoms:...
results leading to a loss of negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
on gastrin secretion. Plasma gastrin concentration is elevated in virtually all individuals with mucolipidosis type IV
Mucolipidosis type IV
Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation...
(mean 1507 pg/mL; range 400-4100 pg/mL) (normal 0-200 pg/mL) secondary to a constitutive achlorhydria. This finding facilitates the diagnosis of patients with this neurogenetic disorder.