Involvement of PACAP in acid-induced HCO3- response in rat duodenums

Pituitary adenylate cyclase activating polypeptides (PACAP) stimulate duode nal HCO3- secretion in the rat. The present study was performed to determin e whether endogenous PACAP is involved in the mechanism of acid-induced HCO 3- response in the duodenum, using a PACAP antagonist, PACAP6-27. Under ure thane anaesthetised conditions, a duodenal loop that was made between the p ylorus and the area just above the outlet of the common bile duct was perfu sed with saline, and the HCO3- secretion was measured at pH 7.0 using a pH- stat method and by adding 10 mM HCl. Duodenal HCO3- secretion was significa ntly stimulated by i.v. administration of PACAP-27 (8 nmol kg(-1)) as well as vasoactive intestinal polypeptide (VIP: 8 nmol kg(-1)). The effect of PA CAP-27 (8 nmol kg(-1)) was equivalent to that induced by prostaglandin E-2 (300 mu g kg(-1), i.v.) and significantly suppressed by either PACAP6-27 (4 0 nmol kg(-1), i.v.) or VIP antagonist (Ac-Tyr(1), D-Phe(2)-VIP: 40 nmol kg (-1), i.v.). These peptide antagonists suppressed duodenal HCO3- secretory response to VIP but did not have any effect on either basal or PGE(2)-stimu lated HCO3- secretion. On the other hand, the duodenal mucosa responded to acidification by increasing HCO3- secretion in a indomethacin-sensitive man ner, and this process was also significantly suppressed by both PACAP6-27 a nd VIP-antagonist. Duodenal damage induced by acid perfusion (100 mM HCl fo r 4 h) was significantly worsened by PACAP6-27, VIP antagonist as well as i ndomethacin at the doses that suppressed acid-induced HCO3- secretion. Thes e findings suggest that PACAP may play a role in local modulation of the du odenal mucosal integrity, by mediating the HCO3- secretory response induced by mucosal acidification. (C) 1998 The Italian Pharmacological Society.