Gastric acid secretion peptide

Histamine receptors were first divided into two subclasses Hi and H2 by Ash and Schild (1966) on the basis that the then known antihistamines did not inhibit histamine-induced gastric acid secretion. The justification for this subdivision was established some years later when Black (see Black et al. 1972) developed drugs, like cimetidine, that affected only the histamine stimulation of gastric acid secretion and had such a dramatic impact on the treatment of peptic ulcers. A recently developed H2 antagonist zolantidine is the first, however, to show significant brain penetration. A further H3 receptor has now been established. It is predominantly an autoreceptor on histamine nerves but is also found on the terminals of aminergic, cholinergic and peptide neurons. All three receptors are G-protein-coupled but little is known of the intracellular pathway linked to the H3 receptor and unlike Hi and H2 receptors it still remains to be cloned. Activation of Hi receptors stimulates IP3 formation while the H2 receptor is linked to activation of adenylate cyclase. 

There are a variety of peptide hormones acting in the gut the gastrins stimulate gastric acid secretion secretin and somatostatin inhibit the production of gastrins. Cholecystokinin and somatostatin can inhibit gastric acid secretion directly, and the former one causes the gall-bladder to contract and thus force bile into the duodenum. 

Secretin inhibits postprandial gastrin release (thus decreasing gastric acid secretion) and increases pancreatic exocrine secretion (e.g. of bicarbonate). The secretin receptor (like the GLP-1 receptor and vasoactive intestinal peptide (VIP) receptor) acts via Gas and cAMP elevation. A plant agonist for the secretin receptor has been isolated from the Thai anti-ulcer plant Croton sublyratus (plau-loi) (Table 5.8). 

Gastrin CCK-B receptor 14- and 17-residue peptide amide with a Glu rich region Stimulate gastric acid secretion Solution-phase and solid-phase V -Fmoc chemistry... 

Glucose-dependent insulinotropic polypeptide is originally known as gastric inhibitory polypeptide (GIP), which is a 42-residue peptide first isolated by Brown and Dryburgh (14). It is secreted from the duodenum and proximal jejunum in response to food. Two major physiological effects of GIP are inhibition of gastric acid secretion and stimulation of insulin release. 

Gastric acid secretion may be regulated by several brain peptides, some of which may enhance secretion, while others may act centrally to inhibit secretion. 

Gaxlric inhibitory peptide (GIP) is a 43-amino-acid polypep-lidc isolated from the duodenum. Secretion of GIP into the blood is stimulated by food. The primary action of GIP is inhibition of gastric acid secretion. Other actions include stimulation of insulin and glucagon. secretion and. stimulation of intestinal secretion. ... 

Hersey. S.J. et al. (1995) Gastric acid secretion. Physiol. Rev.. 75.155-190. antalarmin is a synthetic non-peptide CORTICOTROPHIN-RELEASING factor RECEPTOR ANTAGONIST which is more active at the CRF subtype. It is used as a pharmacological tool, antazoline (ban.inn) (antazoline phosphate [usan] antazollne sulphate imidazolamine phenazoline ... 

The principal actions of these peptides are to stimulate gastric acid secretion, to contract intestinal smooth muscle and to contract or relax a range of vascular tissues. A number of neurons in the enteric and central nervous system are excited. Supposed roles for the peptides include a role as a major excitatory enteric neurotransmitter, in central neuronal processes, particularly in feeding and satiety processes and for GRP include a role in facilitating gastric acid secretion. 

The discovery of the first nonpetide CCK antagonist, the natural product asperlicin, in 1985 (495) shifted the medicinal chemistry focus from peptides to small molecule antagonists (496,497).CCK-B receptors are the dominant isoform in the brain, and antagonists at this subtype are potential anxiolytics. Many CCK-B antagonists also modulate gastric acid secretion through peripheral CCK-B (gastrin) receptors. 

Table. 2. ED50for in vivo stimulation of gastric acid secretion in rats by gastrin and hinge-peptide/gastrin chimeras and their receptor binding affinities in parietal cells isolated from rabbit gastric fundus.

Calcitonin gene-related peptide (CGRP) Enteric neurons and enteroendocrine cells of the rectum Inhibits insulin secretion Oral glucose intake and gastric acid secretion... 

Peptide YY (PYY) Enteroendocrine cells, developing pancreas alpha cells in mature islets 1. Inhibits both gastric acid secretion and gastric motility 2. Slows intestinal motility 3. Inhibits pancreatic exocrine secretion 1. Oral nutrient ingestion 2. Bile acids and fatty acids 3. Amino acids in colon... 

Secretin Enteroendocrine S cells in upper small bowel 1. Stimulates pancreatic and biliary bicarbonate and water secretion 2. Regulates pancreatic enzyme secretion 3. Inhibits postprandial gastric emptying, gastrin release, and gastric acid secretion 1. Gastric acid, bile salts, fatty acids, peptides, and ethanol 2. Somatostatin inhibits secretion... 

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