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 unselective muscarinic antagonist atropine (0.4 mg/kg) inhibited secretion stimulated by bethanechol (15 micrograms.kg-1.h-1) but not that stimulated by carbachol (15 micrograms.kg-1.h-1). The nicotinic antagonist hexamethonium (10 mg.kg-1.h-1), however, abolished the latter response. The muscarinic M1-selective antagonists pirenzepine and telenzepine (0.025, 0.25 and 2.5 mg/kg) did not decrease but caused a dose-dependent rise in duodenal mucosal HCO3- secretion, an effect abolished by cervical vagotomy or infusion of the alpha-adrenoceptor antagonist phentolamine (0.1 mg.kg-1.h-1). Phentolamine alone caused a sustained increase in secretion. McN-A-343 (0.025, 0.25, and 2.5 mg/kg), an M1-selective agonist and ganglionic stimulator, increased the HCO3- secretion; this effect was not prevented by vagotomy but was attenuated by pirenzepine. Intracerebroventricular infusion of pirenzepine and telenzepine did not cause any changes in secretion. These findings suggest that peripheral muscarinic M1 and nicotinic receptors mediate cholinergic stimulation of duodenal mucosal HCO3- secretion. Pirenzepine and telenzepine may act stimulatory by antagonizing muscarinic M1-transmission in peripheral sympathetic ganglia, thus decreasing postsynaptic adrenergic inhibition.
Säfsten
B
B
Department of Physiology and Medical Biophysics, Uppsala University Biomedical Center, Sweden.
Jedstedt
G
G
Flemström
G
G
D000758:Anesthesia; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics / Q000494:pharmacology; D014628:Vagotomy
D001639:Bicarbonates; D010276:Parasympatholytics; D010277:Parasympathomimetics; D013565:Sympatholytics; D010646:Phentolamine