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 those of vasoactive intestinal polypeptide (VIP). Animals were given mepirizole (200 mg/kg, s.c.) for induction of duodenal ulcers, and gastric acid and duodenal HCO3- secretions were measured with or without pretreatment of PACAP-27 or VIP. Mepirizole increased acid secretion and induced hemorrhagic lesions in the proximal duodenum within 6 h. Intravenous bolus injection or infusion of PACAP-27 (4 and 8 nmol/kg or 8 nmol/kg/h) increased duodenal HCO3- secretion even in the presence of mepirizole, without effect on acid secretion, and significantly reduced the severity of duodenal lesions caused by mepirizole. In contrast, VIP (8 nmol/kg, i.v.) given by bolus injection significantly decreased acid secretion induced by mepirizole, in addition to stimulation of HCO3- secretion, and prevented duodenal lesions in response to mepirizole. These results suggest that PACAP-27 increases duodenal HCO3- secretion and this action may be important in maintaining the duodenal mucosal 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 is unknown.
Department of Pharmacology & Experimental Therapeutics Kyoto Pharmaceutical University, Yamashina, Japan.
K
K
Yagi
K
K
Takehara
M
M
Kitamura
K
K
Takeuchi
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D004840:Epirizole / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000627:therapeutic use
C495403:Adcyap1 protein, rat; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001639:Bicarbonates; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D004840:Epirizole