Agouti antagonism of melanocortin binding and action in the B16F10 murine melanoma cell line.

摘要: Several dominant mutations at the murine agouti locus result in expression of a number phenotypic changes, including predominantly yellow coat color, obesity, and hyperinsulinemia. The mutants exhibit ectopic overexpression normal protein, suggesting that regulates coloration by direct antagonism alpha-melanocyte-stimulating hormone receptor. We have tested this hypothesis examining inhibition both melanocortin-stimulated cyclic adenosine monophosphate production binding radioactive melanocortin analog B16F10 melanoma cell line. Inhibition melanocortin-induced nucleotide accumulation did not require preincubation cells with was independent agonist used. Furthermore, to activation receptor could be described simple competitive model similar constants 1.9 0.9 nM, respectively. mutually exclusive verified cross-linking experiments using radiolabeled analog. Competitive can account for effects on suggests possibility other changes observed may due action novel receptor(s).