Cholinergic regulation of guinea pig duodenal bicarbonate secretion.

Although it is well known that vagal stimulation induces duodenal HCO3- secretion, there is presently no information about the nature of the cholinoceptor and the intracellular signals involved. In a series of experiments performed in a guinea pig duodenal loop model in situ, intravenous carbachol, atropine, pirenzepine, and hexamethonium were used to determine the extent of cholinergic stimulation and the types of cholinoceptors. Carbachol (2 micrograms.kg-1.5 min-1) stimulated HCO3- secretion threefold, and atropine (0.1 mg.kg-1.5 min-1) and pirenzepine (1 mg.kg-1.5 min-1) both abolished this effect. In addition, hexamethonium (0.3 mg.kg-1.5 min-1) inhibited carbachol-stimulated duodenal HCO3- secretion. Vasoactive intestinal peptide (VIP, 5 micrograms.kg-1.5 min-1) stimulated duodenal HCO3- secretion, and this action was partly inhibited by atropine (0.1 mg.kg-1.5 min-1) but not by pirenzepine (1 mg.kg-1.5 min-1). [4Cl-D-Phe6,Leu17]VIP (3.3 mg/kg), an antagonist to VIP, reduced basal, VIP-stimulated, and carbachol-stimulated HCO3- secretion. To examine the role of Ca2+ in this process, Ca2+ ionophore A23187, verapamil, and nifedipine were employed. A23187 (5, 50, 500 micrograms.kg-1.5 min-1) stimulated duodenal HCO3- secretion, an effect blocked by the VIP antagonist, and modestly augmented the effect of carbachol. Verapamil (0.2 mg.kg-1.5 min-1) and nifedipine (1.7 mg.kg-1.5 min-1) stopped the effect of carbachol on duodenal HCO3- secretion. These results suggest, that in cholinergic regulation of duodenal HCO3- secretion, the M-cholinoceptor pathway, Ca2+, and VIP are involved.