PERIPHERAL ANALGESIC ACTIVITIES OF PEPTIDES RELATED TO ALPHA-MELANOCYTE STIMULATING HORMONE AND INTERLEUKIN-1-BETA-193-195

1 The hyperalgesic effects of interleukin-1-beta (IL-1-beta) and prostaglandin E2 (PGE2) were measured in rats. 2 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(4),D-Phe7]alpha-MSH >alpha-MSH > Lys-D-Pro-Val > Lys-Pro-Val > Lys-D-Pro-Thr > D-Lys-Pro-Thr. 3 Hyperalgesic responses to PGE, 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. 4 The potencies of [N1(4), D-Phe7]alpha-MSH and alpha-MSH were greatly diminished by deletion of their C-terminal tripeptide, Lys11-Pro-Val13. 5 Nor-binaltorphimine (Nor-BNI) largely reversed the analgesic effects of alpha-MSH, [N1(4), D-Phe7]alpha-MSH, Lys-Pro-Val and LyS-D-Pro-Val indicating that kappa-opioid receptors mediated the analgesic activity of these peptides. 6 Nor-BNI did not antagonize the inhibition by LyS-D-Pro-Thr and D-Lys-Pro-Thr of IL-1-beta evoked hyperalgesia indicating that these peptides were not acting via kappa-opioid receptors.