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 μg · 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 μg · 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 μg · 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.