Somatostatin inhibits gastric acid secretion after gastric mucosal prostaglandin synthesis inhibition by indomethacin in man.

Abstract

SUMMARY The inhibitory effect of indomethacin, 200+200 mg administered per os over 24 hours, on the prostaglandin E2 generative capacity of gastric mucosal tissue was determined in healthy male volunteers. The effect of prostaglandin synthesis inhibition on somatostatin induced suppression of food-stimulated acid secretion was tested. Peptone meal stimulated acid secretion was quantified in five healthy volunteers by intragastric titration with and without indomethacin pretreatment. Somatostatin doses of 200, 400, and 800 pmol/kg/h each significantly inhibited the peptone stimulated acid output. Indomethacin treatment, resulting in 90% inhibition of prostaglandin E2 synthesis, did not affect glucose-or peptone-stimulated acid output or modify the inhibitory action of somatostatin. Clinically, acid inhibition by somatostatin has been used to treat bleeding peptic ulcers. Ulcer haemorrhage may be preceded by an excessive use of drugs that inhibit prostaglandin synthesis such as aspirin or other non-steroidal anti-inflammatory agents. Recent observations in the rat indicate that prostaglandins mediate the inhibitory action of somatostatin on gastric acid secretion. The present results suggest that prostaglandins are not required for inhibition of gastric acid secretion by somatostatin in man.The inhibitory action of somatostatin on gastric acid secretion has been well established in several species including man' and the rat,2 but the mechanism of its action is not fully understood. Observations in the anaesthetised rat indicate that prostaglandins mediate the inhibitory action of somatostatin on gastric acid secretion.2 Thus, somatostatin promoted gastric release of prostaglandin E2, a potent local inhibitor of acid secretion, and indomethacin, a prostaglandin synthesis inhibitor totally blocked the inhibitory action of somatostatin. The present study examines the hypothesis that prostaglandins mediate the inhibitory action of somatostatin on gastric acid secretion also in man. weight 78 kg) in good health and without history of gastrointestinal disorders were studied. The study was approved by the V A Wadsworth Human Studies Committee and informed consent was obtained from each subject. After an overnight fast, a double lumen tube was introduced into the stomach, through which test meals were administered. Liquid meal stimulated gastric acid secretion was quantified by intragastric titration to pH 5.5.3 A 5.5% glucose solution was administered during 30 minutes and followed by four consecutive 8% Bactopeptone (Difco Labs Inc.) meals (45+3x30 min). MethodsAll subjects were studied on three separate days. On one day somatostatin was dissolved in saline containing 0 25% human serum albumin and infused intravenously during the last three peptone meals at sequentially increasing doses each of 30 min duration; 200, 400, and 800 pmol/kg/h. A second day was identical but the subjects were pretreated with a 200 mg dose of indomethacin (Indocin, MSD) per os on the day before and on the morning of the study. A third day w...

Interactions between Antral Peptides and Prostaglandin Biosynthesis in Gastric Acid Regulation in Man

“…In addition to suppressing gastrin release, somatostatin also directly inhibits the pari etal cell [48], Although two studies in the rat suggested that indomethacin interacted with the effect of infused somatostatin on the parietal cell [14,17], repeated efforts to re produce the results in man have been unsuc cessful [21,22], in agreement with the present observations. However, plasma gas trin was not monitored in the previous stud ies.…”

Somatostatin

“…For example, gastric emptying in the dog has been observed to be delayed by somatostatin, but in humans, conflicting data have been reported. Johansson et al (1 11) observed that the early gastric emptying of an oral glucose meal is enhanced by somatostatin, and similar effects were noted by Mogard et al (152). In contrast, Johansson et al (112) have also reported in separate studies that the later phases of gastric emptying are delayed by the peptide.…”

Peptides as Regulators of Gastric Acid Secretion

“…Thus somatostatin may stimulate the release of some as yet unidentified final inhibitory mediator. Prostaglandins do not appear to play a crucial role because cyclo-oxygenase inhibition does not interfere with the inhibitory response (125). The possibility that an intestinal inhibitor distinct from secretin is released by acid from the duodenal bulb has been entertained.…”