Effects of recombinant agouti-signaling protein on melanocortin action.

摘要: Mouse agouti protein is a paracrine signaling molecule that has previously been demonstrated to be an antagonist of melanocortin action at several cloned rodent and human receptors. In this study we report the effects agouti-signaling (ASIP), homolog mouse agouti, on alpha-MSH or ACTH five known receptor subtypes (hMCR 1-5). When stably expressed in L cells (hMC1R, hMC3R, hMC4R, hMC5R) adrenocortical cell line OS3 hMC2R, hMC4R), purified recombinant ASIP inhibits generation cAMP stimulated by (hMC2R). However, dose-response Schild analysis indicated degree inhibition varied significantly among subtypes; potent inhibitor hMC1R, but relatively weak hMC3R hMC5R. These analyses also apparent mechanism antagonism subtypes, with characteristics consistent competitive observed only more complex behavior other these latter receptors, nonetheless, can classified as surmountable (hMC3R, hMC4R nonsurmountable Recombinant inhibited binding radiolabeled melanocortins, [125I-Nle4, D-Phe7] [125I-Phe2, Nle4]ACTH 1-24, hMCR 1-5 relative efficacy paralleled ability inhibit accumulation hMC4R. results provide new insight into biochemical suggest may play important role modulating humans.