ALPHA-2-ADRENOCEPTORS DO NOT REGULATE CATECHOLAMINE SECRETION BY BOVINE ADRENAL-MEDULLARY CELLS - A STUDY WITH CLONIDINE

Abstract

Experiments have been performed with perfused bovine adrenal glands, with freshly isolated chromaffin cells, and with chromaffin cells maintained in tissue culture to investigate the suggestion that there are .alpha.-adrenoceptors present which regulate catecholamine secretion. Only one set of observations has lent support to this suggestion: the rather specific .alpha.2-adrenoceptor agonist clonidine inhibits catecholamine secretion evoked by the physiolgical secretogogue, acetylcholine, and by the related nicotinic agonists, carbachol and nicotine. All other observations detract from the suggestion. Other .alpha.-adrenoceptor agonists (noradrenaline, adrenaline, tramazoline, phenylephrine, and .alpha.-methyl-nor-adrenaline) are virtually ineffective at inhibiting secretion evoked by carbachol. In addition, the .alpha.-adrenoceptor antagonists phentolamine, phenoxybenzamine, and yohimbine not only fail to enhance the secretion of catecholamines evoked by carbachol but also fail to offset the inhibitory action of clonidine. The data suggest that functional .alpha.2-adrenoceptors of the classical type are not present upon bovine chromaffin cells and that, in this tissue, clonidine must act in some other way. In the bovine adrenal medullary chromaffin cell clonidine probably acts at the nicotinic receptor because it does not reduce catecholamine secretion evoked by depolarizing concentrations of potassium or veratridine but does reduce the carbachol-evoked influx or 22Na that can be measured in the presence of tetrodotoxin and ouabain and which probably reflects entry through the nicotine channel. Furthermore, clonidine can abolish, in reversible fashion the acetylcholine-activated inward current determined with patch-clamp.