DISCOVERY OF AN ALPHA-MELANOTROPIN ANTAGONIST EFFECTIVE IN-VIVO

A hybrid analogue, H-His-D-Arg-Ala-TrpD-Phe-Lys-NH2, was designed base d upon the primary structures of a growth hormone-releasing peptide an alogue, [His(1),Lys(6)]GHRP, and the MSH fragment, Ac-alpha-MSH(6-11)- NH2. In vitro studies demonstrated the alpha-MSH antagonistic efficacy of the analogue in the lizards Sceloporus jarrovii and Urosaurus orna tus. In live white background-adapted S. jarrovii previously injected with the antagonist (10 nmol/5 g b.wt.), maximal skin darkening induce d by alpha-MSH was reduced to 50%. In white background-adapted U. orna tus, previous injection of the analogue (1 nmol/5 g b.wt.) totally abo lished the response to alpha-MSH and depressed to 50% the maximal resp onse elicited by the superpotent MSH analogue, [Nle(4),D-Phe(7)]alpha- MSH.