MELANOCYTE-STIMULATING HORMONE INHIBITS GROWTH OF AMELANOTIC CELLS OFHUMAN-MALIGNANT MELANOMA WITH CONCOMITANT CHANGES IN CONCENTRATIONS OF CAMP, PHOSPHATIDYLINOSITOLS, AND INOSITOL PHOSPHATES

Administration of 10(-6)-5.10(-8) M alpha-melanocyte stimulating hormo ne (alpha-MSH) inhibited growth of amelanotic cells of human malignant BRO melanoma and changed the cell morphology without inducing their m elanization or tyrosinase activity. Growth inhibition was associated w ith a considerable increase in intracellular cAMP concentration; the l evel of cGMP remained unchanged Dibutyryl-cAMP and an inhibitor of cAM P-dependent protein kinase A also suppressed cell growth. Administrati on of alpha-MSH increased the concentrations of myo-inositol mono-, di -, and 1,4,5-triphosphate, it also changed phosphatidylinositol kinase and phosphatidylinositol 4-phosphate kinase activities that determine the levels of phosphatidylinositol 4-phosphate and phosphatidylinosit ol 4,5-diphosphate, respectively. Concentrations of myo-inositol phosp hates changed within seconds after alpha-MSH administration and reache d plateaus by 3-5 min; in contrast, cAMP concentrations increased cons iderably by 30 min.