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Am J Physiol Gastrointest Liver Physiol 281: G997-G1003, 2001;
0193-1857/01 $5.00
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Vol. 281, Issue 4, G997-G1003, October 2001

PACAP stimulates gastric acid secretion in the rat by inducing histamine release

Arne K. Sandvik1,2, Guanglin Cui1,2, Ingunn Bakke1,2, Bjørn Munkvold1,2, and Helge L. Waldum2

1 Department of Physiology and Biomedical Engineering and 2 Section of Gastroenterology, Department of Medicine, University Hospital of Trondheim, Faculty of Medicine, The Norwegian University of Science and Technology, N-7489 Trondheim, Norway

Previous studies have shown that pituitary adenylate cyclase-activating peptide (PACAP) stimulates enterochromaffin-like (ECL) cell histamine release, but its role in the regulation of gastric acid secretion is disputed. This work examines the effect of PACAP-38 on aminopyrine uptake in enriched rat parietal cells and on histamine release and acid secretion in the isolated vascularly perfused rat stomach and the role of PACAP in vagally (2-deoxyglucose) stimulated acid secretion in the awake rat. PACAP has no direct effect on the isolated parietal cell as assessed by aminopyrine uptake. PACAP induces a concentration-dependent histamine release and acid secretion in the isolated stomach, and its effect on histamine release is additive to gastrin. The histamine H2 antagonist ranitidine potently inhibits PACAP-stimulated acid secretion without affecting histamine release. Vagally stimulated acid secretion is partially inhibited by a PACAP antagonist. The results from the present study strongly suggest that PACAP plays an important role in the neurohumoral regulation of gastric acid secretion. Its effect seems to be mediated by the release of ECL cell histamine.

pituitary adenylate cyclase-activating peptide; enterochromaffin-like cell; parietal cell; vagus


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