Continuous exposure to nitric oxide enhances diazepam binding inhibitor mRNA expression in mouse cerebral cortical neurons.
Effects of sustained exposure to nitric oxide (NO) formed by long-term activation of N-methyl-D-aspartate (NMDA) receptors and liberated from a long-lasting NO generator, DETA NONOate, on diazepam binding inhibitor (DBI) and its mRNA expressions were examined using mouse cerebral cortical neurons. Long-term exposure to NMDA increased DBI mRNA expression, and NO synthase inhibitors dose-dependently inhibited this increase. DETA NONOate dose-dependently increased DBI mRNA expression when exposing the neurons to this agent for 3 days and a maximal enhancement of the expression was found at 100 microM of the NO generator. In addition, a significant increase in DBI mRNA expression was observed 1 day after the exposure to 100 microM DETA NONOate, and the maximal expression was observed 2 days after the exposure, whereas transient exposure for less than 3 h to 100 microM DETA NONOate produced no changes in the expression. DETA NONOate (100 microM)-induced increase in DBI mRNA expression was completely abolished by concomitant exposure to hemoglobin. DBI content was also dose-dependently increased by DETA NONOate after the exposure for 3 days. The inhibition of cGMP formation by 1H-[1,2,4] oxadiazolo [4,3-alpha]quinoxalin-1-one (ODQ) showed no affects on the DETA NONOate-induced expression, suggesting that the increased expression of DBI mRNA is mediated via processes independent of cGMP. These results indicate that continuous exposure of the neurons to NO is an essential factor for increasing DBI mRNA expression in the neurons.