Intrathecal administration of p-hydroxymercuribenzoate or phosphoramidon/bestatin-combined induces antinociceptive effects through different opioid mechanisms.
The antinociceptive effect of intrathecally (i.t.) administered protease inhibitors was tested against capsaicin (800 ng) injected into the dorsal surface of a hindpaw. Both p-hydroxymercuribenzoate (2-8 nmol), a cysteine protease inhibitor, and phosphoramidon (1-4 nmol), an endopeptidase 24.11 inhibitor in the presence of bestatin (0.25 nmol) an aminopeptidase inhibitor, administered i.t. 60 min prior to the injection of capsaicin produced a dose-dependent reduction of the capsaicin-induced paw licking and biting response. p-Hydroxymercuribenzoate (4 nmol)-induced antinociception was significantly antagonized by nor-binaltorphimine, a selective kappa-opioid receptor antagonist, but not by naltrindole, a selective delta-opioid receptor antagonist. On the other hand, phosphoramidon (4 nmol) /bestatin-induced antinociception was significantly antagonized by naltrindole, but not by nor-binaltorphimine. The results indicate that the antinociceptive effect of p-hydroxymercuribenzoate may be due to the inhibition of a cysteine protease degrading endogenous dynorphins whereas phosphoramidon in the presence of bestatin blocks the degradation of enkephalins.
Tan-No
K
K
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Taira
A
A
Inoue
M
M
Ohshima
K
K
Sakurada
T
T
Sakurada
C
C
Nylander
I
I
Demuth
H U
HU
Silberring
J
J
Terenius
L
L
Tadano
T
T
Kisara
K
K
D000818:Animals; D002211:Capsaicin; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006020:Glycopeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006614:Hindlimb; D006902:Hydroxymercuribenzoates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007278:Injections, Spinal; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011957:Receptors, Opioid / Q000502:physiology*; D013997:Time Factors
D004338:Drug Combinations; D006020:Glycopeptides; D006902:Hydroxymercuribenzoates; D009292:Narcotic Antagonists; D011480:Protease Inhibitors; D011957:Receptors, Opioid; C030601:4-hydroxymercuribenzoate; C051844:norbinaltorphimine; D009271:Naltrexone; C055382:naltrindole; D007930:Leucine; C012211:ubenimex; D002211:Capsaicin; C008890:phosphoramidon