INVOLVEMENT OF PACAP IN ACID-INDUCED HCO₃⁻RESPONSE IN RAT DUODENUMS

Abstract

Pituitary adenylate cyclase activating polypeptides (PACAP) stimulate duodenal HCO₃⁻secretion in the rat. The present study was performed to determine whether endogenous PACAP is involved in the mechanism of acid-induced HCO₃⁻response in the duodenum, using a PACAP antagonist, PACAP6-27. Under urethane anaesthetised conditions, a duodenal loop that was made between the pylorus and the area just above the outlet of the common bile duct was perfused with saline, and the HCO₃⁻secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mmHCl. Duodenal HCO₃⁻secretion was significantly 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 PACAP-27 (8 nmol kg⁻¹) was equivalent to that induced by prostaglandin E₂(300 μg kg⁻¹, i.v.) and significantly suppressed by either PACAP6-27 (40 nmol kg⁻¹, i.v.) or VIP antagonist (Ac-Tyr¹,d-Phe²-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 PGE₂-stimulated HCO₃⁻secretion. On the other hand, the duodenal mucosa responded to acidification by increasing HCO₃⁻secretion in a indomethacin-sensitive manner, and this process was also significantly suppressed by both PACAP6-27 and VIP-antagonist. Duodenal damage induced by acid perfusion (100 mmHCl for 4 h) was significantly worsened by PACAP6-27, VIP antagonist as well as indomethacin at the doses that suppressed acid-induced HCO₃⁻secretion. These findings suggest that PACAP may play a role in local modulation of the duodenal mucosal integrity, by mediating the HCO₃⁻secretory response induced by mucosal acidification.