Cholinergic regulation of guinea pig duodenal bicarbonate secretion

Abstract

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.

Na+/Ca2+ exchange regulates Ca2+-dependent duodenal mucosal ion transport and HCO3− secretion in mice

“…Several studies have shown that the nonselective muscarinic antagonist atropine inhibits the stimulation of muscosal HCO 3 Ϫ secretion by carbachol in rats (23,33) and guinea pigs (29) in vivo, as well as in rabbit duodenal mucosa in vitro (15). In our study, atropine abolished carbachol-induced increases in mouse duodenal mucosal I sc and HCO 3 Ϫ secretion, suggesting that these are specific responses likely occurring via stimulation of muscarinic receptors on mouse duodenocytes. ]…”

Stimulation by nizatidine, a histamine H2-receptor antagonist, of duodenal HCO3-secretion in rats: relation to anti-cholinesterase activity

“…Vasoactive intestinal polypeptide (VIP) is the most likely humoral factor mediating the HCO 3 -secretory response to acid, because it is a potent stimulant of duodenal HCO 3 -secretion and is released from nerve endings during the exposure of duodenal mucosa to acid [17] . Odes et al [32] reported that acetylcholine increases a release of VIP from enteric nerves via both muscarinic M 1 and M 3 receptors, which in turn stimulates HCO 3 -secretion in the duodenum. Since nizatidine significantly potentiated the HCO 3 -response to acetylcholine, it is possible that the acid-induced HCO 3 -secretion is also enhanced by the anti-AChE activity in the presence of nizatidine.…”

Stimulatory Effect of Nitric Oxide on Bicarbonate Secretion in Bullfrog Duodenums in vitro

“…A variety of substances, including prostaglandin (PG) E 2 (PGE 2 ), vasoactive intestinal peptide and theophyline, have been shown to stimulate the HCO – 3 secretion in both in vivo and in vitro [3, 4, 5, 6]. These agents increase intracellular levels of adenosine-3′,5′-cyclic monophosphate (cAMP) by stimulating the adenylate cyclase or inhibiting the phosphodiesterase [6], suggesting that cAMP has a mediator role in duodenal HCO – 3 secretion.…”