Characterization of alkaline response induced by cholinergic agents in the rat duodenum: involvement of M2 receptors and the calcium-dependent process.
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.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Niida
H
H
Okabe
S
S
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008297:Male; D010277:Parasympathomimetics / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001626:Bethanechol Compounds; D001639:Bicarbonates; D010277:Parasympathomimetics; D011458:Prostaglandins E; D018723:Bethanechol; D002217:Carbachol