Role of gastrin, histamine, and acetylcholine in the gastric phase of acid secretion in anesthetized rats

Kevin C K Lloyd, Helen E Raybould, Y. Tache, J. H. Walsh

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56 Scopus citations

Abstract

To determine the relative contributions of gastrin, histamine, and cholinergic stimulation to the gastric phase of acid secretion, peptone- stimulated acid output was measured in urethan-anesthetized pylorus-ligated rats after intravenous administration of gastrin monoclonal antibody, cimetidine, and atropine. Intragastric peptone stimulated acid secretion four-fold over basal, which was associated with a significant increase in plasma gastrin levels. Gastrin immunoneutralization and simultaneous H2- and muscarinic-receptor blockade demonstrated that ~40% of peptone-stimulated acid output was attributed to endogenous gastrin through a histamine- dependent pathway, whereas 20% of acid output was accounted for by a cholinergic component. Another 10% of titratable acid was omeprazole- insensitive and presumably due to intragastric digestion of peptone. Therefore, ~30% residual acid output in response to peptone could not be accounted for by known acid stimulatory mechanisms. In rats given somatostatin monoclonal antibody to block the tonic inhibitory effect of endogenous somatostatin, residual acid output was a similar fraction of meal- stimulated acid output. In contrast, gastric distension induced by intragastric instillation of saline stimulated acid secretion to 1.5-fold over basal. Although 60% of distension-induced acid secretion could be inhibited by either H2 blockade or gastrin immunoneutralization, acid output returned to basal levels after simultaneous muscarinic blockade. These results indicate that gastrin, through a histaminergic pathway, is the principal mediator of meal-stimulated acid secretion in anesthetized rats. Approximately 30% of acid output was due to other unidentified mechanisms, such as chemical secretagogues, a direct effect of amino acids, or novel peptides.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume262
Issue number4 25-4
StatePublished - 1992

Keywords

  • anticholinergic
  • atropine
  • cimetidine
  • gastric physiology
  • gastrin monoclonal antibody
  • H antagonist
  • immunoneutralization
  • omeprazole
  • peptone
  • somatostatin monoclonal antibody
  • urethan anesthesia

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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