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 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.
Poole
S
S
Division of Endocrinology, National Institute for Biological Standards and Control, Potters Bar, Herts.
Bristow
A F
AF
Lorenzetti
B B
BB
Das
R E
RE
Smith
T W
TW
Ferreira
S H
SH
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D000521:alpha-MSH / Q000494:pharmacology*
D000700:Analgesics; D004731:Endotoxins; D007375:Interleukin-1; D010455:Peptides; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D000521:alpha-MSH; D009271:Naltrexone; D015232:Dinoprostone