Shibasaki Masahiro, Katsura Masashi, Tsujimura Atsushi, Ohkuma Seitaro
Department of Pharmacology, Kawasaki Medical School, Matsushima 577, Kurashiki 701-0192, Japan.
Life Sci. 2006 Dec 14;80(2):166-72. doi: 10.1016/j.lfs.2006.08.036. Epub 2006 Sep 12.
Mechanisms of increase in diazepam binding inhibitor (DBI) mRNA expression in mouse cerebrocortical neurons after sustained morphine exposure were investigated. Increases in DBI and its mRNA expressions induced by sustained morphine (0.3 microM) exposure for 3 days were completely abolished by naloxone and nifedipine, but not by omega-agatoxin VIA and omega-conotoxin GIVA. Increase in [(3)H]diltiazem binding to the particulate fractions from the morphine-treated neurons was due to increased B(max) value with no changes in K(d) value. Western blot analysis on L-type high voltage-gated calcium channel (HVCC) subunits revealed the increased expressions of alpha1C, alpha1D, and alpha2/delta1 subunits and decreased of beta4 subunit expression, whereas expression of N- and P/Q-type HVCC subunits was not changed. These results indicate that morphine-induced increase in DBI mRNA expression is mediated via increased Ca(2+) entry through up-regulated L-type HVCCs.
研究了持续吗啡暴露后小鼠大脑皮质神经元中地西泮结合抑制剂（DBI）mRNA表达增加的机制。持续吗啡（0.3微摩尔）暴露3天诱导的DBI及其mRNA表达增加被纳洛酮和硝苯地平完全消除，但未被ω-芋螺毒素VIA和ω-芋螺毒素GIVA消除。[3H]地尔硫䓬与吗啡处理神经元的微粒体部分结合增加是由于Bmax值增加，而Kd值无变化。对L型高电压门控钙通道（HVCC）亚基的蛋白质印迹分析显示，α1C、α1D和α2/δ1亚基的表达增加，β4亚基的表达减少，而N型和P/Q型HVCC亚基的表达未改变。这些结果表明，吗啡诱导的DBI mRNA表达增加是通过上调的L型HVCCs增加Ca2+内流介导的。
