title: Nonadrenergic modulation by clonidine of the cosecretion of catecholamines and enkephalins in adrenal chromaffin cells.
abstract: Cultured bovine chromaffin cells cosecrete catecholamines and enkephalins following cholinergic nicotinic stimulation. Initial reports on the inhibitory effect of clonidine on catecholamine secretion raised the possibility of a modulation of chromaffin cell function through a presynaptic adrenergic mechanism. The purpose of this work was to investigate the pharmacological characteristics of this inhibitory effect of clonidine on the cosecretion of catecholamines and enkephalins in 4-day-old cultured chromaffin cells. We observed that clonidine completely inhibits nicotine-stimulated secretion of both leucine-enkephalin and catecholamines with an IC50 of 34 microM. Treatment of chromaffin cells for 3 days with 100 nM reserpine leads to a 67% increase in nicotine-stimulated secretion of leucine-enkephalin without any effect on the IC50 of clonidine. In reserpine-treated chromaffin cells, norepinephrine (100 microM) inhibits only by 27% nicotine-stimulated secretion of leucine-enkephalin with an IC50 of 50 microM. Neither the alpha 2-adrenergic antagonist yohimbine nor the alpha 1-adrenergic antagonist prazosin could fully reverse the inhibitory effect of clonidine on leucine-enkephalin secretion at 10 nM. These results tend to rule out the role of alpha-adrenergic receptors in the mediation of clonidine inhibition of cosecretion in chromaffin cells.
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D004743:Enkephalin, Leucine; D009538:Nicotine; D012110:Reserpine; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine