Q. Write Short Notes on Gastrin, CCK, and Secretin
Gastrin is produced by cells called G cells in the antral portion of the gastric mucosa. G cells are flasked shapes, with a broad base containing many gastric granules and a narrow apex that reaches the mucosal surface.
Gastrin is typical of a number of polypeptide hormones in that it shows both macroheterogenicity and microheterogenicity.
Macroheterogenicity refers to the occurrence in tissues and body fluids of peptide chains of various lengths; microheterogenicity refers to differences in molecular structure due to derivatization of single amino acid residues.
Preprogastrin is processed into fragments of various sizes. Three main fragments contain 34, 17, and 14 amino acids residues.
However, all that can be said at present is that G17 is the principal form with respect to gastric acid secretion. G14 and G17 have half-lives of 2 to 3 min in the circulation, whereas G34 has a half-life of 15 min. Gastrin are inactivated primarily in the kidney and small intestine.
Physiologic Actions: In large doses, gastrin has a variety of actions, but its principal physiologic actions are stimulation of gastric acid and pepsin secretion and stimulation of the growth of the mucosa of the stomach and small and large intestines (trophic action).
Regulation of Secretion: Gastrin secretion is affected by the contents of the stomach, the rate of discharge of the vagus nerves, and blood-borne factors.
Gastrin secretion is also increased by the presence of the products of protein digestion in the stomach, particularly amino acids, which act directly on the G cells. Phenylalanine and tryptophan are particularly effective.
Acid n the antrum inhibits gastrin secretion, partly by a direct action on G cells and partly by release of somatostatin, a relatively potent inhibitor of gastrin secretion. The effect of acid is the basis of a negative feedback loop regulating gastrin secretion. Increased secretion of the hormone increases acid secretion, but the acid then feed back to inhibit further gastrin secretion.
In conditions such as pernicious anemia in which the acid-secreting cells of the stomach are damaged, gastrin secretion is chronically elevated.
Atropine does not inhibit the gastrin response to a test meal in humans, because the transmitter secreted by the postganglionic vagal fibers that innervate the G cells is gastrin-releasing polypeptide (GRP) rather than acetylcholine.
Cholecystokinin (CCK) is secreted by cells in the mucosa of the upper small intestine.
Physiologic Actions: It has a plethora of actions in the gastrointestinal system, but the most important appears to be the stimulation of pancreatic enzyme secretion, the contraction of the gallbladder (the action for which it was named), and relaxation of the sphincter of Oddi, which allows both bile and [pancreatic juice to flow into the intestinal lumen.
In addition to its primary actions, CCK augments the action of secretin in producing secretion of an alkaline pancreatic juice. It also inhibits gastric emptying, exerts a trophic effect on the pancreas, increases the synthesis of enterokinase, and may enhance the motility of the small intestine and colon.
Like gastrin, CCK shows both macroheterogenicity and microheterogenicity. Prepro-CCK is processed into many fragments.
Regulation of secretion: The secretion of CCK is increased by contact of the intestinal mucosa with the products of digestion, particularly peptides and amino acids, and by their presence in the duodenum of fatty acids containing more than 10 carbon atoms.
Because the bile ad pancreatic juice that enter the duodenum in response to CCK further the digestion of protein and fat, and the products of this digestion stimulate further CCK secretion, a sort of positive feedback operates in the control of the secretion of this hormone. However, the positive feedback is terminated when the products of digestion move on to lower portions of the gastrointestinal tract.
Secretin is secreted by S cells that are located deep in the glands of the mucosa of the upper portion of the small intestine. The structure of secretin is different from that of gastrin and CCK, but similar to that of glucagon, VIP, and GIP.
Physiologic Actions: secretin increases the secretion of bicarbonate by the duct cells of the pancreas and biliary tract. It does causes the secretion of a watery, alkaline pancreatic juice. Its action on pancreatic duct cells is mediated via cAMP. Secretin also augments the action of CCK in producing pancreatic secretion of digestive enzymes. It decreases gastric acid secretion and may cause contraction of the pyloric sphincter.
Regulation of secretion: The secretion of secretin is increased by the products of protein digestion and by acid bathing the mucosa of the upper small intestine. The release of secretin by acid is another example of feedback control. Secretin causes alkaline pancreatic juice to flood into the duodenum, neutralizing the acid from the stomach and thus inhibiting further secretion of the hormone.