Discovery of an alpha-melanotropin antagonist effective in vivo.
A hybrid analogue, H-His-D-Arg-Ala-Trp-D-Phe-Lys-NH2, was designed based upon the primary structures of a growth hormone-releasing peptide analogue, [His1,Lys6]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 ornatus. In live white background-adapted S. jarrovii previously injected with the antagonist (10 nmol/5 g b.wt.), maximal skin darkening induced by alpha-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 alpha-MSH and depressed to 50% the maximal response elicited by the superpotent MSH analogue, [Nle4,D-Phe7]alpha-MSH.
Castrucci
A M
AM
Departamento de Fisiologia, Universidade de São Paulo, Brasil.
Sherbrooke
W C
WC
Sawyer
T K
TK
Staples
D J
DJ
Tuma
M C
MC
Hadley
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D008116:Lizards / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D000521:alpha-MSH / Q000037:antagonists & inhibitors*
D009842:Oligopeptides; C090018:histidyl-arginyl-alanyl-tryptophyl-phenylalanyl-lysinamide; D000521:alpha-MSH