STIMULATORY EFFECT OF PACAP ON GASTRODUODENAL BICARBONATE SECRETION IN RATS

The effects of pituitary adenylate cyclase activating polypeptides (PA CAPs) on gastroduodenal HCO3- secretion were investigated in anestheti zed rats and compared with those of vasoactive intestinal polypeptide (VIP). Under urethane anesthesia. a rat stomach mounted in an ex vivo chamber (in the absence of acid secretion) or a rat proximal duodenal loop was perfused with saline, and the HCO3- secretion was measured at pH 7.0 using a pa-stat method and by adding 10 mM HCl. Intravenous in jection of PACAP-27 stimulated HCO3- secretion in a dose-dependent man ner in the duodenum but not in the stomach; at 8 nmol/kg PACAP-27 incr eased the HCO3- secretion to maximal values of four times greater than basal levels, although this peptide had no effect on duodenal HCO3- s ecretion after intracisternal administration (1 nmol/rat). PGE(2) (300 mu g/kg, iv) significantly increased HCO3- secretion in both the stom ach and the duodenum. The potency of duodenal HCO3- secretory action w as in the following order; PACAP-27 > PACAP-38 = VIP, and that of PACA P-27 was about 100-fold greater than that of PGE(2). The duodenal HCO3 - secretory action of PACAP-27 as well as PGE(2) was markedly potentia ted by prior administration of isobutylmethyl xanthine (10 mg/kg, sc), the inhibitor of phos phodiesterase. Folskolin (250 mu g/kg, iv), the stimulator of adenylate cyclase, also increased HCO3- secretion in th e duodenum but not in the stomach. These results suggest that: 1) PACA Ps are potent stimulators of HCO3- secretion in the duodenum but not i n the stomach; 2) this action is mediated by cAMP through stimulation of adenylate cyclase; 3) cAMP is a mediator in duodenal but not gastri c HCO3- secretion; and 4) PACAPs may be involved in the peripheral reg ulation of duodenal HCO3- secretion.