Peripheral analgesic activities of peptides related to alpha-melanocyte stimulating hormone and interleukin-1 beta 193-195

Br J Pharmacol. 1992 Jun;106(2):489-92. doi: 10.1111/j.1476-5381.1992.tb14361.x.


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 greater than alpha-MSH greater than Lys-D-Pro-Val greater than Lys-Pro-Val greater than Lys-D-Pro-Thr greater than D-Lys-Pro-Thr. 3. Hyperalgesic responses to PGE2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Analgesics / pharmacology*
  • Animals
  • Dinoprostone / pharmacology
  • Endotoxins / pharmacology
  • Escherichia coli
  • Interleukin-1 / pharmacology*
  • Male
  • Molecular Sequence Data
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Peptides / pharmacology*
  • Peripheral Nerves / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, kappa / drug effects
  • alpha-MSH / pharmacology*


  • Analgesics
  • Endotoxins
  • Interleukin-1
  • Peptides
  • Receptors, Opioid, kappa
  • norbinaltorphimine
  • alpha-MSH
  • Naltrexone
  • Dinoprostone