Nitrous oxide antinociception in BXD recombinant inbred mouse strains and identification of quantitative trait loci.

Among inbred mouse strains, DBA/2 mice are unique because of their poor responsiveness to nitrous oxide (N2O) antinociception. As a first step towards identifying candidate genes involved in determining antinociceptive responsiveness to N2O, male mice from the DBA/2 strain, the more responsive C57BL/6 strain, their B6D2F1 offspring, and 22 BXD recombinant inbred (RI) strains derived from DBA/2 and C57BL/6 mice were exposed to N2O and evaluated using the acetic acid abdominal constriction test. When exposed to 70% N2O, C57BL/6, DBA/2 and B6D2F1 mice exhibited antinociceptive responses of 78, 22 and 55%, respectively.

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.

Nitrous oxide anxiolytic effect in mice in the elevated plus maze: mediation by benzodiazepine receptors.

In earlier research, we have hypothesized that exposure to nitrous oxide (N2O) produces an anxiolytic effect that is mediated by benzodiazepine (BZ) receptors. The present research was conducted to characterize pharmacologically the behavioral effects of N2O in comparison with a BZ standard, chlordiazepoxide (CP), in the mouse elevated plus maze. Exposure to increasing levels of N2O produced a concentration-related increase in the percent of total entries into and the percent of total time spent on the open arms, a pattern of response similar to that induced by CP.

Conversion of spironolactone to 7 alpha-thiomethylspironolactone by hepatic and renal microsomes.

Recent observations indicate that 7 alpha-thiomethylspironolactone is an important circulating metabolite of the mineralocorticoid antagonist spironolactone (SL). Studies were carried out to determine possible sites and pathways of 7 alpha-thiomethyl-SL formation and, in particular, to evaluate SL metabolism by guinea pig hepatic and renal microsomal preparations. In the absence of S-adenosylmethionine (SAM), liver and kidney microsomes rapidly converted SL to 7 alpha-thio-SL as the only metabolite.