title: PACAP stimulates gastric acid secretion in the rat by inducing histamine release.
abstract: 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.
authors.affiliation: Department of Physiology and Biomedical Engineering, University Hospital of Trondheim, Faculty of Medicine, The Norwegian University of Science and Technology, N-7489 Trondheim, Norway. arne.sandvik@medisin.ntnu.no
authors.forename: A K
authors.initials: AK
authors.lastname: Sandvik
authors.forename: G
authors.initials: G
authors.lastname: Cui
authors.forename: I
authors.initials: I
authors.lastname: Bakke
authors.forename: B
authors.initials: B
authors.lastname: Munkvold
authors.forename: H L
authors.initials: HL
authors.lastname: Waldum
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula; D005753:Gastric Mucosa / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D013270:Stomach / Q000166:cytology / Q000187:drug effects*
chemical_list: C495401:ADCYAP1 protein, human; C495403:Adcyap1 protein, rat; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006635:Histamine H2 Antagonists; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010726:Phosphodiesterase Inhibitors; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D000632:Aminopyrine; D011899:Ranitidine; D003847:Deoxyglucose; D015056:1-Methyl-3-isobutylxanthine