Involvement of nitric oxide in intracerebroventricular β-endorphin-induced neuronal release of methionine-enkephalin

Abstract

Previous work has suggested that the antinociceptive effect of nitrous oxide (N 2O) in rats is mediated, at least in part, by β-endorphin (β-EP) and that centrally administered β-EP stimulates release of methionine-enkephalin (ME) in the rat spinal cord. Since inhibition of central nitric oxide (NO) production has been found to suppress N 2O antinociception, we examined the possible involvement of NO in the release of spinal cord ME by i.c.v. β-EP. Urethane-anesthetized, male Sprague-Dawley rats were intrathecally (i.t.) perfused with artificial cerebrospinal fluid (aCSF) and fractions of perfusate were assayed for immunoreactive (i.r.) ME. The β-EP-induced increase in ME concentration in the i.t. perfusate was significantly suppressed by perfusing the animal with aCSF containing 100 μM L-N G-nitro arginine (L-NOARG), an inhibitor of NO synthase (NOS). The further addition of 50 μM 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 μM failed to produce a greater suppression of the β-EP-induced increase in ME. These findings suggest that NO may mediate the β-Ep-induced release of ME in the spinal cord and that interference with this mechanism might be an explanation for the antagonism of N 2O antinociception in rats by NOS inhibitors.