Nonadrenergic modulation by clonidine of the cosecretion of catecholamines and enkephalins in adrenal chromaffin cells.
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.
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
D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D004743:Enkephalin, Leucine; D009538:Nicotine; D012110:Reserpine; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine