Both nicotinic and muscarinic receptors mediate catecholamine secretion by isolated guinea-pig chromaffin cells.
We have studied the roles of nicotinic and muscarinic receptors in the acetylcholine-evoked secretion of catecholamine from guinea-pig chromaffin cells. Isolated guinea-pig chromaffin cells secrete catecholamine in response to acetylcholine, nicotine, and a variety of muscarinic agonists. Optimal concentrations of acetylcholine (50-200 microM) induce the release of 10-25% of the catecholamine content of the cells in 10 min. Maximal secretion evoked by nicotine or by muscarinic agonists is 5-12% of the catecholamine content of the cells. Secretion evoked by optimal concentrations of nicotine (50 microM) and muscarine (200 microM) are additive, and together these agonists cause catecholamine release equivalent to that produced by optimal concentrations of acetylcholine. Atropine causes a biphasic inhibition of acetylcholine-induced catecholamine secretion; low concentrations of atropine (0.02-0.01 microM) inhibit by 35-45% the catecholamine secretion evoked by 100 microM acetylcholine. Increasing the atropine concentration from 0.1 to 5 microM causes no further decrease in acetylcholine-evoked release, but at concentrations above 5 microM, a second distinct phase of inhibition appears. At 100 microM, atropine reduces acetylcholine-evoked secretion by 85%. At 0.1 microM, atropine significantly inhibits secretion induced by muscarinic, but not nicotinic, agonists. Tubocurarine (50 microM) does not block muscarinic stimulation of release, but inhibits acetylcholine- and nicotine-evoked release by 70 and 80%, respectively. Our experiments indicate that nicotinic and muscarinic stimulation represent distinct mechanisms for the activation of catecholamine release from guinea-pig chromaffin cells.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002845:Chromatography; D006168:Guinea Pigs; D010277:Parasympathomimetics / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D014403:Tubocurarine / Q000494:pharmacology
D002395:Catecholamines; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D001285:Atropine; D014403:Tubocurarine