Intrathecal administration of thiorphan and bestatin enhances the antinociception and release of Met-enkephalin induced by beta-endorphin intraventricularly in anesthetized rats.
Effects of bestatin and thiorphan administered intrathecally, on inhibition of the tail-flick response and the release of Met-enkephalin induced by beta-endorphin administered intraventricularly were studied in anesthetized rats. Intrathecal pretreatment with 100 micrograms of thiorphan or bestatin potentiated the inhibition of the tail-flick response induced by beta-endorphin injected intraventricularly in pentobarbital anesthetized rats; the ED50 values for beta-endorphin were decreased 5- and 7-fold by thiorphan and bestatin, respectively. To determine if the potentiating effect was due to the inhibition of the degradation of Met-enkephalin released by intraventricular beta-endorphin, the effects of intrathecal perfusion with thiorphan or bestatin on the release of immunoreactive Met-enkephalin from the spinal cord by intraventricular injection of beta-endorphin were studied. beta-Endorphin injected into the 4th ventricle at a dose of 5 micrograms increased immunoreactive Met-enkephalin in the spinal perfusate in urethane-anesthetized rats. Thiorphan or bestatin (1 x 10(-7) to 1 x 10(-4) M each) increased the amount of immunoreactive Met-enkephalin released by intraventricular beta-endorphin in a dose-dependent manner. The results provide additional evidence for the hypothesis that antinociception induced by beta-endorphin is mediated by release of Met-enkephalin.
Suh
H H
HH
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Tseng
L L
LL
D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000758:Anesthesia; D000818:Animals; D004744:Enkephalin, Methionine / Q000378:metabolism*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D013623:Tail; D015244:Thiorphan / Q000494:pharmacology*; D001615:beta-Endorphin / Q000494:pharmacology*
D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D015244:Thiorphan; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex