PACAPs stimulate duodenal bicarbonate secretion at PACAP receptors in the rat.
We investigated the effects of pituitary adenylate cyclase-activating polypeptides (PACAPs) on gastroduodenal HCO(3)- secretion in anesthetized rats and characterized their effects by comparison with the effects of vasoactive intestinal polypeptide (VIP). Under urethan anesthesia, a rat proximal duodenal loop or a rat stomach mounted in an ex vivo chamber (in the absence of acid secretion) was perfused with saline, and HCO(3)- 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 HCO(3)- secretion in a dose-dependent manner in the duodenum, but not in the stomach, although this peptide had no effect on duodenal HCO(3)- secretion after intracisternal administration. The duodenal HCO(3)- stimulatory action was similarly observed after intravenous administration of PACAP-38 and VIP, and the potency of action was in the following order: PACAP-27 > PACAP-38 = VIP. The duodenal HCO(3)- stimulatory action of PACAP-27 was potentiated by pretreatment with 3-isobutyl-1-methylxanthine, similar to that of prostaglandin E2, and was significantly attenuated by PACAP-(6--27) (PACAP antagonist) or Ac-Tyr1,D-Phe2-VIP (VIP antagonist) but was not affected by bilateral vagotomy or prior administration of atropine, verapamil, and indomethacin. Forskolin, the stimulator of adenylate cyclase, also increased HCO(3)- secretion in the duodenum, but not in the stomach. These results suggest that 1) PACAP is a potent stimulator of HCO(3)- secretion in the duodenum, but not in the stomach, and may be involved in the peripheral regulation of duodenal HCO(3)- secretion, 2) this action is mediated by adenosine 3',5'-cyclic monophosphate, probably through PACAP and VIP receptors, and 3) adenosine 3',5'-cyclic monophosphate is a mediator in duodenal, but not in gastric, HCO(3)- secretion.
Takeuchi
K
K
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Japan.
Takehara
K
K
Kato
S
S
Yagi
K
K
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D014628:Vagotomy; D014630:Vagus Nerve; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D001639:Bicarbonates; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D014660:Vasoactive Intestinal Peptide; D001285:Atropine; D014700:Verapamil; D000242:Cyclic AMP; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin