The association between the melanocyte-stimulating hormone receptor and the alpha 2-adrenoceptor on the Anolis melanophore.

1 The primary effect of catecholamines was to lighten Anolis skin previously darkened by alpha-melanocyte-stimulating hormone (alpha-MSH). In concentrations above 10(-7) M noradrenaline, 10(-6) M adrenaline and 10(-5) dopamine, darkening of subpopulations of melanophores occurred. Subsequent experiments were concerned with the effect of low catecholamine concentrations on alpha-MSH action. 2 The relationship between MSH receptors and alpha-adrenoceptors on the Anolis melanophore was studied by a kinetic approach using the rate bioassay method and by use of alpha-adrenoceptor agonists and antagonists. 3 alpha-MSH dose-response curves were shifted, in parallel, to the right in the presence of the catecholamines, noradrenaline, adrenaline and dopamine, and Lineweaver-Burke plots and Arunlakshana-Schild plots indicated that the catecholamines antagonized MSH action by a competitive mechanism. 4 Phentolamine had an inhibitory effect on the action of adrenaline but not on the action of MSH. Therefore MSH and catecholamine actions were mediated by separate receptors. 5 The classical kinetics of competition are not confined to competition at a single receptor. 6 The alpha-adrenoceptor was defined as the alpha 2-subtype since (a) the alpha 2-selective agonist, clonidine, was found to mimic catecholamine action. (b) The alpha 2-selective antagonist, yohimbine, blocked the actions of clonidine and adrenaline. (c) The alpha 1-selective antagonist, prazosin, had negligible blocking effects on adrenaline and clonidine. 7 We conclude that a close association exists between the separate MSH receptor and alpha 2-adrenoceptor on the Anolis melanophore. The competition that takes place between MSH and catecholamines must occur after hormone-receptor interaction, possibly through a common adenylate cyclase moiety oppositely controlled by the two receptors involved.