Katsura M, Ohkuma S, Jun X, Kuriyama K
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Eur J Pharmacol. 1996 Feb 29;298(1):71-7. doi: 10.1016/0014-2999(95)00764-4.
Effect of exposure of primary cultured cerebral cortical neurons to ethyl beta-carboline-3-carboxylate (beta-CCE) on the function of benzodiazepine receptors was studied. Exposure of neurons to beta-CCE (0.1-10 microM) decreased the binding of [3H]flunitrazepam to extensively washed membrane fractions in a dose- and time-dependent manner, whereas the binding of [3H]flunitrazepam to the cytosolic fractions increased (180%) under the same conditions as described above. Ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a] [1,4] benzodiazepine-3-carboxylate (Ro15-1788), an antagonist of the central type of benzodiazepine receptors, completely abolished the beta-CCE-induced decrease in [3H]flunitrazepam binding and the IC50 value for [3H]flunitrazepam binding to the extensively washed membrane fractions prepared from beta-CCE-treated neurons was similar to that from non-treated neurons. Scatchard analysis revealed that only the Bmax value for [3H]flunitrazepam binding decreased after the exposure to beta-CCE (1 microM) for 12 h, although the Kd value was not altered. These results indicate that beta-CCE induces the down-regulation of benzodiazepine receptors by an increase in benzodiazepine receptor internalization.
研究了原代培养的大脑皮质神经元暴露于β-咔啉-3-羧酸乙酯（β-CCE）对苯二氮䓬受体功能的影响。将神经元暴露于β-CCE（0.1 - 10 microM）以剂量和时间依赖性方式降低了[³H]氟硝西泮与充分洗涤的膜组分的结合，而在上述相同条件下，[³H]氟硝西泮与胞质组分的结合增加（180%）。苯二氮䓬受体中央型拮抗剂乙基-8-氟-5,6-二氢-5-甲基-6-氧代-4H-咪唑并[1,5-a][1,4]苯二氮䓬-3-羧酸酯（Ro15 - 1788）完全消除了β-CCE诱导的[³H]氟硝西泮结合减少，并且β-CCE处理的神经元制备的充分洗涤的膜组分上[³H]氟硝西泮结合的IC50值与未处理神经元的相似。Scatchard分析显示，暴露于β-CCE（1 microM）12小时后，仅[³H]氟硝西泮结合的Bmax值降低，而Kd值未改变。这些结果表明，β-CCE通过增加苯二氮䓬受体内化诱导苯二氮䓬受体下调。
