INVOLVEMENT OF NITRIC-OXIDE IN INTRACEREBROVENTRICULAR BETA-ENDORPHIN-INDUCED NEURONAL RELEASE OF METHIONINE-ENKEPHALIN

Previous work has suggested that the antinociceptive effect of nitrous oxide (N2O) in rats is mediated, at least in part, by beta-endorphin (beta-EP) and that centrally administered beta-EP stimulates release o f methionine-enkephalin (ME) in the rat spinal cord. Since inhibition of central nitric oxide (NO) production has been found to suppress N2O antinociception, we examined the possible involvement of NO in the re lease of spinal cord ME by i.c.v. beta-EP. Urethane-anesthetized, male Sprague-Dawley rats were intrathecally (i.t.) perfused with artificia l cerebrospinal fluid (aCSF) and fractions of perfusate were assayed f or immunoreactive (i.r.) ME. The beta-EP-induced increase in ME concen tration in the i.t. perfusate was significantly suppressed by perfusin g the animal with aCSF containing 100 mu M L-N-G-nitro arginine (L-NOA RG), an inhibitor of NO synthase (NOS). The further addition of 50 mu M L-arginine (L-ARG), but not D-arginine (D-ARG), to the aCSF reversed the suppression of the ME change by L-NOARG. However, the potency of L-ARG decreased with increasing concentrations of L-ARG. On the other hand, increasing the concentration of L-NOARG in the aCSF to 250 mu M failed to produce a greater suppression of the beta-EP-induced increas e in ME. These findings suggest that NO may mediate the beta-EP-induce d release of ME in the spinal cord and that interference with this mec hanism might be an explanation for the antagonism of N2O antinocicepti on in rats by NOS inhibitors.