Stimulatory effect of PACAP on gastroduodenal bicarbonate secretion in rats.
The effects of pituitary adenylate cyclase activating polypeptides (PACAPs) on gastroduodenal HCO3- secretion were investigated in anesthetized 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 pH-stat method and by adding 10 mM HCl. Intravenous injection of PACAP-27 stimulated HCO3- secretion in a dose-dependent manner in the duodenum but not in the stomach; at 8 nmol/kg PACAP-27 increased the HCO3- secretion to maximal values of four times greater than basal levels, although this peptide had no effect on duodenal HCO3- secretion after intracisternal administration (1 nmol/rat). PGE2 (300 micrograms/kg, iv) significantly increased HCO3- secretion in both the stomach and the duodenum. The potency of duodenal HCO3- secretory action was in the following order; PACAP-27 > PACAP-38 = VIP, and that of PACAP-27 was about 100-fold greater than that of PGE2. The duodenal HCO3- secretory action of PACAP-27 as well as PGE2 was markedly potentiated by prior administration of isobutylmethyl xanthine (10 mg/kg, sc), the inhibitor of phosphodiesterase. Folskolin (250 micrograms/kg, iv), the stimulator of adenylate cyclase, also increased HCO3- secretion in the duodenum but not in the stomach. These results suggest that: 1) PACAPs are potent stimulators of HCO3- secretion in the duodenum but not in the stomach; 2) this action is mediated by cAMP through stimulation of adenylate cyclase; 3) cAMP is a mediator in duodenal but not gastric HCO3- secretion; and 4) PACAPs may be involved in the peripheral regulation of duodenal HCO3- secretion.
Takeuchi
K
K
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.
Yagi
K
K
Kitamura
M
M
Kobayashi
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D001639:Bicarbonates; D009479:Neuropeptides; D010726:Phosphodiesterase Inhibitors; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine