CHOLINERGIC INFLUENCE ON DUODENAL MUCOSAL BICARBONATE SECRETION IN THE ANESTHETIZED RAT

Bicarbonate secretion by duodenum distal to the Brunner's glands area was titrated in situ in rats anesthetized with thiobarbiturate. The un selective muscarinic antagonist atropine (0.4 mg/kg) inhibited secreti on stimulated by bethanechol (15 mu g.kg(-1).h(-1)) but not that stimu lated by carbachol (15 mu g.kg(-1).h(-1)). The nicotinic antagonist he xamethonium (10 mg.kg(-1).h(-1)), however, abolished the latter respon se. The muscarinic M(1)-selective antagonists pirenzepine and telenzep ine (0.025, 0.25 and 2.5 mg/kg) did not decrease but caused a dose-dep endent rise in duodenal mucosal HCO3- secretion, an effect abolished b y cervical vagotomy or infusion of the alpha-adrenoceptor antagonist p hentolamine (0.1 mg.kg(-1).h(-1)). Phentolamine alone caused a sustain ed increase in secretion. McN-A-343 (0.025, 0.25, and 2.5 mg/kg), an M (1)-selective agonist and ganglionic stimulator, increased the HCO3- s ecretion; this effect was not prevented by vagotomy but was attenuated by pirenzepine. Intracerebroventricular infusion of pirenzepine and t elenzepine did not cause any changes in secretion. These findings sugg est that peripheral muscarinic M(1) and nicotinic receptors mediate ch olinergic stimulation of duodenal mucosal HCO3- secretion. Pirenzepine and telenzepine may act stimulatory by antagonizing muscarinic M(1)-t ransmission in peripheral sympathetic ganglia, thus decreasing postsyn aptic adrenergic inhibition.