Cholinergic influence on duodenal bicarbonate response to hydrochloric acid perfusion in the conscious rat.

Abstract

Present information suggests that endogenous prostaglandins, hormonal factors, and neuropeptides participate in the regulation of duodenal bicarbonate secretion in response to luminal hydrochloric acid. The purpose of this study was to examine the effects of cholinergic antagonists and agonists on basal and acid-stimulated bicarbonate secretion in the proximal duodenum of the conscious rat. The basal bicarbonate secretion, 9 mumol X cm-1 X h-1, increased to 21 +/- 3 mumol X cm-1 X h-1 after 5 min of exposure to 150 mM HCl and remained significantly elevated for more than 3.5 h. The muscarinic blocker atropine, 0.5 mg X kg-1, reduced the acid-stimulated bicarbonate response by a third, and higher doses did not increase the inhibition. The ganglionic blocker hexamethonium, 10-20 mg X kg-1, suppressed in a dose-related manner the alkaline response by maximally one half. The opioid inhibitor naloxone was also an effective inhibitor. Hexamethonium, but not atropine, inhibited the basal duodenal bicarbonate secretion, which was unaffected by graded doses of the cholinergic agonists bethanechol and carbachol. We conclude that cholinergic nicotinic activity participates in maintaining basal duodenal bicarbonate secretion in the conscious rat. The bicarbonate response to luminal 150 mM HCl is partially dependent on cholinergic sites, but activation of such sites is not a single final step, since cholinergic agonists failed to elevate bicarbonate secretion from basal.