Involvement of PACAP in acid-induced HCO3- response in rat duodenums.
Pituitary adenylate cyclase activating polypeptides (PACAP) stimulate duodenal HCO3- secretion in the rat. The present study was performed to determine whether endogenous PACAP is involved in the mechanism of acid-induced HCO3- response in the duodenum, using a PACAP antagonist, PACAP6-27. Under urethane anaesthetised conditions, a duodenal loop that was made between the pylorus and the area just above the outlet of the common bile duct 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. Duodenal HCO3- secretion was significantly stimulated by i.v. administration of PACAP-27 (8 nmol kg-1) as well as vasoactive intestinal polypeptide (VIP: 8 nmol kg-1). The effect of PACAP-27 (8 nmol kg-1) was equivalent to that induced by prostaglandin E2 (300 micrograms kg-1, i.v.) and significantly suppressed by either PACAP6-27 (40 nmol kg-1, i.v.) or VIP antagonist (Ac-Tyr1, D-Phe2-VIP: 40 nmol kg-1, i.v.). These peptide antagonists suppressed duodenal HCO3- secretory response to VIP but did not have any effect on either basal or PGE2-stimulated HCO3- secretion. On the other hand, the duodenal mucosa responded to acidification by increasing HCO3- secretion in a indomethacin-sensitive manner, and this process was also significantly suppressed by both PACAP6-27 and VIP-antagonist. Duodenal damage induced by acid perfusion (100 mM HCl for 4 h) was significantly worsened by PACAP6-27, VIP antagonist as well as indomethacin at the doses that suppressed acid-induced HCO3- secretion. These findings suggest that PACAP may play a role in local modulation of the duodenal mucosal integrity, by mediating the HCO3- secretory response induced by mucosal acidification.
Takeuchi
K
K
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.
Yagi
K
K
Sugamoto
S
S
Furukawa
O
O
Kawauchi
S
S
D000758:Anesthesia; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004347:Drug Interactions; D004386:Duodenum / Q000502:physiology* / Q000601:surgery; D006851:Hydrochloric Acid / Q000009:adverse effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000494:pharmacology*