Exposure to nitrous oxide stimulates a nitric oxide-dependent neuronal release of beta-endorphin in ventricular-cisternally-perfused rats.
We have previously shown that the antinociceptive effect of nitrous oxide (N(2)O) in the rat hot plate test is sensitive to antagonism by antisera against the endogenous opioid peptide beta-endorphin. Moreover, N(2)O-induced antinociception is reduced by inhibition of nitric oxide (NO) production in the brain. To test the hypothesis that N(2)O might stimulate an NO-dependent neuronal release of beta-endorphin, we conducted a ventricular-cisternal perfusion with artificial cerebrospinal fluid (aCSF) in urethane-anesthetized Sprague-Dawley rats. Ten-minute fractions of aCSF perfusate were collected from separate groups of room air-exposed rats, N(2)O-exposed rats, and L-NAME-pretreated, N(2)O-exposed rats; they were then analyzed for their content of NO metabolites and beta-endorphin. Compared to room air control, exposure to 70% N(2)O increased perfusate levels of the NO metabolites nitrite and nitrate as well as beta-endorphin. Pretreatment of rats with L-N(G)-nitro arginine methyl ester, an inhibitor of NO synthase, prevented the N(2)O-induced increases in nitrite, nitrate and beta-endorphin. These findings demonstrate in an in vivo rat model that N(2)O may stimulate an NO-dependent neuronal release of beta-endorphin.
Zelinski
Lisa M
LM
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, P.O. Box 646534, Pullman, WA 99164, USA.
Ohgami
Yusuke
Y
Quock
Raymond M
RM
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D002408:Catheters, Indwelling; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009609:Nitrous Oxide / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin / Q000134:cerebrospinal fluid*
D018712:Analgesics, Non-Narcotic; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D001615:beta-Endorphin; D009609:Nitrous Oxide; D019331:NG-Nitroarginine Methyl Ester