Coordinated action of calcium ion and adenosine 3',5'-monophosphate upon the release of alpha-melanocyte-stimulating hormone from the intermediate lobe of the rat pituitary gland.

Stimulation of the release of alpha MSH from dispersed rat melanotrophs by L-isoproterenol, 8-bromo-cAMP, or cholera toxin requires calcium ion (Ca++) in the incubation medium; the stimulatory effect of each of these agents is attenuated by D-600, a Ca++ antagonist. In contrast, stimulation of the formation of cAMP by L-isoproterenol, isobutyl methylxanthine, or cholera toxin does not require Ca++ in the incubation medium. Ca++ diminishes the amount of cAMP formed by cholera toxin-treated melanotrophs. Ca++ inhibits adenylate cyclase activity and enhances cyclic nucleotide phosphodiesterase activity in cell-free homogenates of intermediate lobe tissue. A23187, a calcium ionophore, increases the accumulation of 45Ca by melanotrophs and enhances the release of alpha MSH. Furthermore, when tested upon cholera toxin-treated melanotrophs, A23187 potentiates the Ca++-induced inhibition of cAMP formation. The results indicate that Ca++ is essential for the release of alpha MSH, and that cAMP in some way enhances the effects of Ca++ upon the release process.