EFFECTS OF PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE-27 ON ALKALINE SECRETORY AND MUCOSAL ULCEROGENIC RESPONSES IN RAT DUODENUM

Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on duodenal mucosal HCO3- secretion and ulcerogenic responses induced by mepirizole in anesthetized rats were examined and compared with tho se of vasoactive intestinal polypeptide (VIP). Animals were given mepi rizole (200 mg/kg, s.c.) for induction of duodenal ulcers, and gastric acid and duodenal HCO3- secretions were measured with or without pret reatment of PACAP-27 or VIP. Mepirizole increased acid secretion and i nduced hemorrhagic lesions in the proximal duodenum within 6 h. Intrav enous bolus injection or infusion of PACAP-27 (4 and 8 nmol/kg or 8 nm ol/kg/h) increased duodenal HCO3- secretion even in the presence of me pirizole, without effect on acid secretion, and significantly reduced the severity of duodenal lesions caused by mepirizole. In contrast, VI P (8 nmol/kg, i.v.) given by bolus injection significantly decreased a cid secretion induced by mepirizole, in addition to stimulation of HCO 3- secretion, and prevented duodenal lesions in response to mepirizole . These results suggest that PACAP-27 increases duodenal HCO3- secreti on and this action may be important in maintaining the duodenal mucosa l integrity against acid, and VIP affords duodenal protection by both increasing duodenal HCO3- secretion and decreasing acid secretion. The reason for the different effects of PACAP and VIP on acid secretion i s unknown.