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 of 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 release of spinal cord ME by i.c.v. beta-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 beta-EP-induced increase in ME concentration in the i.t. perfusate was significantly suppressed by perfusing the animal with aCSF containing 100 microM L-NG-nitro arginine (L-NOARG), an inhibitor of NO synthase (NOS). The further addition of 50 microM 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 microM failed to produce a greater suppression of the beta-EP-induced increase in ME. These findings suggest that NO may mediate the beta-EP-induced release of ME in the spinal cord and that interference with this mechanism might be an explanation for the antagonism of N2O antinociception in rats by NOS inhibitors.
Hara
S
S
Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford 61107-1897, USA.
Kuhns
E R
ER
Ellenberger
E A
EA
Mueller
J L
JL
Shibuya
T
T
Endo
T
T
Quock
R M
RM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000378:metabolism*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D019335:Nitroarginine; D009569:Nitric Oxide; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D001120:Arginine