Biodegradation of alpha-MSH and derived peptides by rat brain extracts, and by rat and human serum

The peptides alpha-MSH and MSH/ACTH 4-10 were degraded by rat brain extracts and serum to yield free amino acids among the end-products. Breakdown of these two peptides was double that of a related synthetic hexapeptide Met (0)-Glu-His-Phe-D-Lys-Phe. No significant breakdown of the hexapeptide occurred after incubation with human serum; it also had almost negligible pigmentary effects in vivo and in vitro when compared to alpha-MSH. The patterns of amino acid release indicate possible endopeptidase cleavage at Phe-Arg in alpha-MSH followed by secondary exopeptidase action to release free amino acids. For the hexapeptide, the primary cleavage point occurred at the -His3-Phe4 bond. The stability of this analog in human sera, coupled with its lower rate of degradation in the CNS, may contribute to its more potent behavioral actions in vivo.