Calcium and Guanosine Nucleotide Modulation of Melanotropin Receptor Function and Adenylate Cyclase in the M2R Melanoma Cell Line
Melanocytes are specialized melanin producing cells of neural embryonic origin, which function to regulate cutaneous pigmentation in vertebrate systems (Parker, 1981), Both α- and β-melanotropins (α-MSH, β-MSH) are thought to regulate melanin synthesis in these cells via cAMP-dependent stimulation of the enzyme, tyrosinase (monophenol monooxygenase), in direct correlation with adenylate cyclase (AC) activity (Johnson and Pastan, 1972; Varga et al., 1974: O’Keefe and Cuatrecasas, 1974). Calcium has been implicated in the actions of both melanotropic hormones (Vesely and Hadley, 1974; Van de Veerdonk and Brouwer, 1973), as well as for adrenocorticotropin (ACTH) (Bar and Hechter, 1969; Sayers et al, 1972; Perchellet and Sharma, 1979), on the stimulation of AC activity, though the specific step(s) in the cyclase pathway that require calcium have not been adequately elucidated. Recently, several reports have shown that millimolar levels of extracellular free calcium are important for both ACTH binding and subsequent corticosteroid secretion in rat adrenal cortical cells (Cheitlin et al., 1985), and for photoaffinity labeling and subsequent melanophore dispersion in Xenopus, using photoreactive α-MSH (De Graan et al., 1982a; De Graan et al., 1982b). However, in these studies the direct activation of hormone-sensitive adenylate cyclase, as a consequence of hormone binding, was not examined.
KeywordsAdenylate Cyclase Free Calcium Adenylate Cyclase Activity cAMP Accumulation Free Calcium Concentration
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