Discovery of an α-melanotropin antagonist effective in vivo

Abstract

A hybrid analogue, H-His- d-Arg-Ala-Trp- d-Phe-Lys-NH 2, was designed based upon the primary structures of a growth hormone-releasing peptide analogue, [His 1,Lys 6]GHRP, and the MSH fragment, Ac-α-MSH(6–11)-NH 2. In vitro studies demonstrated the α-MSH antagonistic efficacy of the analogue in the lizards Sceloporus jarrovii and Urosaurus ornatus. In live white background-adapted S. jarrovii previously injected with the antagonist (10 nmol/5 g b.wt.), maximal skin darkening induced by α-MSH was reduced to 50%. In white background-adapted U. ornatus, previous injection of the analogue (1 nmol/5 g b.wt.) totally abolished the response to α-MSH and depressed to 50% the maximal response elicited by the superpotent MSH analogue, [Nle 4, d-Phe 7]α-MSH.