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The following evidence suggests that cyclic AMP is the mediator of MSH-induced darkening of the frog skin: 1. When added to the isolated frog skin, exogenous cyclic AMP mimicked the action of α-MSH in causing reversible dispersion of melanin granules in melanophores with resultant darkening of the skin. 2. α-MSH stimulated both cyclic AMP formation and darkening in dorsal skin but stimulated neither response in ventral skin. 3. Graded concentrations of α-MSH produced graded increases in cyclic AMP levels in the dorsal frog skin. 4. α-MSH, β-MSH and ACTH brought about increased cyclic AMP concentration in dorsal frog skin with the same relative potencies as they exhibited in stimulating frog skin darkening. 5. The increased cyclic AMP levels occurred at least as fast as darkening in response to α- MSH. 6. Theophylline (a known inhibitor of the cyclic 3′,5′-nucleotide phosphodiesterase which catalyzes cyclic AMP to 5′-AMP) acted synergistically with α-MSH in increasing the dorsal skin content of cyclic AMP. 7. Norepinephrine diminished the effectiveness of α-MSH with respect to both cyclic AMP concentrations and darkening of the dorsal skin of the frog. (Endocrinology 84: 362,1969)
Abe et al. (Sat,) studied this question.