Peripheral analgesic activities of peptides related to alpha -melanocyte stimulating hormone and interleukin-1 beta

The hyperalgesic effects of interleukin-1 beta (IL-1 beta ) and prostaglandin E sub(2) (PGE sub(2)) were measured in rats. Hyperalgesic responses to IL-1 beta were inhibited in a dose-dependent manner by alpha -melanocyte stimulating hormone ( alpha -MSH)-related peptides with the following order of potency: (N1 super(4),D-Phe super(7)) alpha -MSH> alpha -MSH>Lys-D-Pro-Val>Lys-Pro-Val>Lys-D-Pro-Thr>D-Lys-Pro-Thr. Hyperalgesic responses to PGE sub(2) were not inhibited by Lys-D-Pro-Thr and D-Lys-Pro-Thr but were inhibited in a dose-dependent manner by the other peptides with the same order of potency as against IL-1 beta . The potencies of (N1 super(4), D-Phe super(7)) alpha -MSH and alpha -MSH were greatly diminished by deletion of their C-terminal tripeptide, Lys super(11)-Pro-Val super(13).