Antinociceptive effects of the enkephalinase inhibitor, SCH 34826, in the snail, Cepaea nemoralis.
In vertebrates the effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 (enkephalinase), which cleaves the Gly-Phe bonds in both methionine- and leucine-enkephalin. SCH 34826 ((S)-N-[n-[1-[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine-B-alanine) is a potent, highly specific, enkephalinase inhibitor that has marked analgesic effects in mammals. The present study examined the effects of SCH 34826 on opioid-mediated aversive thermal (nociceptive) response of an invertebrate, the land snail, Cepaea nemoralis. SCH 34828 had significant, dose-related antinociceptive effects in Cepaea that were reduced by naloxone and completely blocked by the specific data opiate antagonist, ICI-174,864, and only weakly affected by the specific kappa opiate antagonist nor-binaltrophimine. These findings with SCH 34826 suggest that an enkephalinase similar to that in vertebrates is present and involved in the mediation of opioid (enkephalin) activity in the snail, Cepaea.
Saksida
L M
LM
Department of Psychology, University of British Columbia, Vancouver, Canada.
Galea
L A
LA
Kavaliers
M
M
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004148:Dioxolanes / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D010146:Pain / Q000503:physiopathology; D012908:Snails / Q000502:physiology*
D000700:Analgesics; D004148:Dioxolanes; D004151:Dipeptides; D009292:Narcotic Antagonists; C056319:Sch 34826; D009270:Naloxone; C051844:norbinaltorphimine; D004743:Enkephalin, Leucine; D009271:Naltrexone; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D015260:Neprilysin