Characterization of alkaline response induced by cholinergic agents in the rat duodenum: involvement of M2 receptors and the calcium-dependent process

K Takeuchi, H Niida and S Okabe

Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.

Duodenal pH, potential difference and acid-neutralizing capacity (HCO3- output) were measured in anesthetized rats, in an attempt to characterize these responses induced by cholinergic agents. When the proximal duodenum (1.7 cm) was perfused at a flow rate of 1 ml/min with saline adjusted to pH 4.5, the pH, potential difference and HCO3- output were 5.2 to 5.5, -3 to -5 mV (mucosa negative) and 1.5 to 1.8 muEq/10 min, respectively. Both carbachol (4 micrograms/kg, i.v.) and bethanechol (100 micrograms/kg, i.v.) significantly elevated all these parameters at the doses that stimulated gastric acid secretion; the net HCO3- output caused by these agents was about 35% of that produced by prostaglandin E2 (300 micrograms/kg, i.v.). These responses induced by carbachol were significantly inhibited by pretreatment with verapamil (0.2 mg/kg, i.v.), a Ca channel blocker, and atropine (0.1 mg/kg, i.v.), a nonselective M1 and M2 antagonist, while they remained unaltered in the presence of pirenzepine (1 mg/kg, i.v.), a selective M1 antagonist, or indomethacin (5 mg/kg, s.c.). However, the effects of prostaglandin E2 on duodenal pH, potential difference and HCO3- output were not significantly affected by any of these agents. These results suggest that the cholinergic agents stimulate HCO3- output in the duodenum, probably mediated by M2 receptors and through the Ca- dependent and electrogenic processes. Endogenous prostaglandins may not be involved in this mechanism.

Volume 254, Issue 2, pp. 465-470, 08/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

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