Acid secretion, inhibition

INTRODUCTION Mechanism of gastric acid secretion Inhibition of gastric acid secretion Therapeutic value of gastric acid inhibition... 

Polyphenols, plant-based nutrients that play a role in decreasing the risk of numerous diseases, also appear to play an important role in ulcer prevention. Animal studies have shown that several different polyphenols help prevent PUD by increasing the formation of gut-protecting mucus decreasing acid secretion inhibiting the growth of H. pylori and... 

EP3 Kidney, adrenal gland, stomach, uterus, testis, ovary, hrain, spleen, colon, heart, liver, skeletal muscle, lung Inhibition of gastric acid secretion, inhibition of water absorption, uterine contraction... 

In contrast to the other cells in the gastric mucosa, the D cell has inhibitory muscarinic receptors of either the M or WL, subtype, allowing the conclusion that vagal stimulation of acid secretion inhibits somatostatin release. 

Biologica.1 Activities a.ndAna.logues, The many pharmacological actions of neurotensin include hypotension, increased vascular permeabihty, hyperglycemia, increased intestinal motility, and inhibition of gastric acid secretion (120). In the brain, it produces analgesia at remarkably low doses (121). 

Fiber components are the principal energy source for colonic bacteria with a further contribution from digestive tract mucosal polysaccharides. Rate of fermentation varies with the chemical nature of the fiber components. Short-chain fatty acids generated by bacterial action are partiaUy absorbed through the colon waU and provide a supplementary energy source to the host. Therefore, dietary fiber is partiaUy caloric. The short-chain fatty acids also promote reabsorption of sodium and water from the colon and stimulate colonic blood flow and pancreatic secretions. Butyrate has added health benefits. Butyric acid is the preferred energy source for the colonocytes and has been shown to promote normal colonic epitheUal ceU differentiation. Butyric acid may inhibit colonic polyps and tumors. The relationships of intestinal microflora to health and disease have been reviewed (10). 

It was known that the K+ -competitive imidazopyridine compound, SCH28080, inhibits acid secretion. Then, many reversible inhibitors were developed. These contain protonatable nitrogens but have a variety of core structures such as imidazopyiidines, piperidinopyr-idines, substituted 4-phenylaminoquinolines, pyrrolo [3,2-c]quinolines, guanidinothiazoles, and 2,4-diamino-pyrimidine derivatives. Several reversible inhibitors have been in clinical trials. 

Fellenius E, Berglindh T, Sachs Getal(1981) Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase. Nature 290 159-161... 

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. 

The search for specific inhibitors of gastric H,K-ATPase has a dual purpose. First, with the help of suitable inhibitors it is possible to get insight into the molecular mechanisms of H,K-ATPase, and second, a specific inhibitor might be clinically useful for inhibition of gastric acid secretion in anti-ulcer therapy. 

Prostaglandins, one of the most important epithelial growth factors, inhibit gastric acid secretion and have numerous mucosal protective effects, the most important of which include the stimulation of both mucus and phospholipid production, promotion of bicarbonate secretion, and increased mucosal cell turnover. Damage to the mucosal defense system is the primary method by which HP or NSAIDs cause peptic ulcers. 

Misoprostol is a synthetic prostaglandin E2 analog that exogenously replaces prostaglandin stores. The minimum effective dose shown to inhibit acid secretion and promote mucosal defense is 400 meg/day. Misoprostol use is limited by a high frequency of bothersome gastrointestinal effects such as abdominal pain, flatulence, and diarrhea. In placebo-controlled studies diarrhea occurred with twice the frequency in the... 

The anti-ulcer agents omeprazole, lanzoprazole, and pantoprazole have been introduced during the past decade for the treatment of peptic ulcers. Gastric acid secretion is efficiently reduced by prazole inhibition of H+K+-ATPase in the parietal cells of the gastrointestinal mucosa [75]. The prazoles themselves are not active inhibitors of the enzyme, but are transformed to cyclic sulfenamides in the intracellular acidic compartment of parietal cells [76]. The active inhibitors are permanent cations at pH < 4, with limited possibilities of leaving the parietal cells, and thus are retained and activated at the site of action. In the neutral body compartments the prazoles are stable, and only trace amounts are converted to the active drugs. (For a review on omeprazole, see Ref. [77].)... 

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