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Evidence has previously been published indicating that melanocyte stimulating hormone (MSH) acts on the frog skin to increase intracellular concentrations of adenosine 3′,5′- monophosphate (cyclic AMP) and that this nucleotide in turn mediates the action of MSH in causing dispersion of melanin granules with consequent darkening of the frog skin. In the present study both norepinephrine and melatonin were found to inhibit the increase in cyclic AMP levels in response to MSH, and both agents prevented or reversed MSH-induced darkening of frog skin. Neither agent had any effect on frog skin darkening induced by exogenous cyclic AMP or on the in vitro enzymatic degradation of cyclic AMP. The inhibitory effects of norepinephrine on the actions of MSH were prevented by the α-adrenergic blocking agents dihydroergotamine and phentolamine, but these drugs were ineffective against melatonin. In contrast, the β-adrenergic agent isoproterenol had no significant inhibitory effect on MSH-induced cyclic AMP accumulation, and the marked inhibitory effect of norepinephrine could not be prevented by α-adrenergic blocking agents. It is concluded that norepinephrine and melatonin both inhibit the action of MSH by preventing the formation of cyclic AMP in response to this hormone. Since the inhibitory effect of norepinephrine can be prevented by α-adrenergic blocking agents while the effect of melatonin cannot, it is inferred that the action of norepinephrine is mediated by an α-adrenergic receptor while that of melatonin might be mediated by a different type of receptor. Both types of receptors, nevertheless, seem to be closely related to adenyl cyclase. These data lend support to the hypothesis that α-adrenergic responses in general might be mediated by decreases in intracellular concentrations of cyclic AMP. (Endocrinology85: 674, 1969)
Abe et al. (Wed,) studied this question.