PACAPS STIMULATE DUODENAL BICARBONATE SECRETION AT PACAP RECEPTORS INTHE RAT

We investigated the effects of pituitary adenylate cyclase-activating polypeptides (PACAPs) on gastroduodenal HCO3- secretion in anesthetize d rats and characterized their effects by comparison with the effects of vasoactive intestinal poly-peptide (VIP). Under urethan anesthesia, a rat proximal duodenal loop or a rat stomach mounted in an ex vivo c hamber (in the absence of acid secretion) was perfused with saline, an d HCO3- secretion was measured at pH 7.0 using a pH-stat method and by addition of 10 mM HCl. Intravenous injection of PACAP-27 stimulated H CO3- secretion in a dose-dependent manner in the duodenum, but not in the stomach, although this peptide had no effect on duodenal HCO3- sec retion after intracisternal administration. The duodenal HCO3- stimula tory action was similarly observed after intravenous administration of PACAP-38 and VIP, and the potency of action was in the following orde r: PACAP-27 > PACAP-38 = VIP. The duodenal HCO3- stimulatory action of PACAP-27 was potentiated by pretreatment with 3-isobutyl-1-methylxant hine, similar to that of prostaglandin E(2), and was significantly att enuated by PACAP-(6-27) (PACAP antagonist) or Ac-Tyr(1),D-Phe(2)-VIP ( VIP antagonist) but was not affected by bilateral vagotomy or prior ad ministration of atropine, verapamil, and indomethacin. Forskolin, the stimulator of adenylate cyclase, also increased HCO3- secretion in the duodenum, but not in the stomach. These results suggest that 1) PACAP is a potent stimulator of HCO3- secretion in the duodenum, but not in the stomach, and may be involved in the peripheral regulation of duod enal HCO3- secretion, 2) this action is mediated by adenosine 3',5'-cy clic monophosphate, probably through PACAP and VIP receptors, and 3) a denosine 3',5'-cyclic monophosphate is a mediator in duodenal, but not in gastric, HCO secretion.