Inhibition of spinal nitric oxide synthase by N(omega)-nitro-L-arginine blocks the release of Met-enkephalin and antinociception induced by supraspinally administered beta-endorphin in the rat.
The antinociception induced by beta-endorphin given supraspinally has been demonstrated previously to be mediated by the release of Met-enkephalin acting on delta2-opioid receptors in the spinal cord. The present study was designed to determine the role of nitric oxide in the spinal cord on beta-endorphin-induced release of Met-enkephalin and antinociception. The experiments were performed in pentobarbital-anesthetized rats. The release of Met-enkephalin was performed using a spinal cord perfusion technique and the Met-enkephalin released in the spinal perfusates was measured by radioimmunoassay. Antinociception was assessed by the tail-flick test. beta-Endorphin (2 microg) given intraventricularly induced the release of Met-enkephalin from the spinal cord. The release of Met-enkephalin was dose-dependently attenuated by N(omega)-nitro-L-arginine (0.1 nM-1 microM) added into spinal perfusates and the attenuation was reversed by intrathecally applied L-arginine. The stereoisomer N(omega)-nitro-D-arginine given intrathecally, however, did not inhibit the release of Met-enkephalin induced by intraventricularly administered beta-endorphin. beta-Endorphin (4 microg) given intraventricularly produced antinociception in rats pretreated intrathecally with saline. The antinociception induced by beta-endorphin was blocked by intrathecally administered N(omega)-nitro-L-arginine (5 microg) and the blockade of antinociception was reversed by intrathecal injection of L-arginine (50 microg). N(omega)-Nitro-D-arginine (5 microg) given intrathecally did not block the intraventricularly administered beta-endorphin-induced antinociception. N(omega)-Nitro-L-arginine (10 microg) given intraventricularly did not affect intraventricularly administered beta-endorphin-induced Met-enkephalin release nor did it affect intraventricular beta-endorphin-induced antinociception, indicating that the effect of N(omega)-nitro-L-arginine is not at supraspinal sites. Intrathecal pretreatment with N(omega)-nitro-L-arginine did not affect intrathecally administered [D-Ala2]deltorphin II-induced antinociception. Our results indicate that N(omega)-nitro-L-arginine given intrathecally attenuates intraventricular beta-endorphin-administered inhibition of the tail-flick response by presynaptically inhibiting the release of Met-enkephalin.
Tseng
L F
LF
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, U.S.A.
Wang
H Q
HQ
Xu
J Y
JY
D000700:Analgesics / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism; D001615:beta-Endorphin / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000700:Analgesics; D004791:Enzyme Inhibitors; D009842:Oligopeptides; C060209:deltorphin II, Ala(2)-; D019335:Nitroarginine; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D019001:Nitric Oxide Synthase