Irwin R P, Maragakis N J, Rogawski M A, Purdy R H, Farb D H, Paul S M
Section on Molecular Pharmacology, NIMH, NINDS, Bethesda, MD 20892.
Neurosci Lett. 1992 Jul 6;141(1):30-4. doi: 10.1016/0304-3940(92)90327-4.
The ability of the neuroactive steroid pregnenolone sulfate to alter N-methyl-D-aspartate (NMDA) receptor-mediated elevations in intracellular Ca2+ ([Ca2+]i) was studied in cultured fetal rat hippocampal neurons using microspectrofluorimetry and the Ca2+ sensitive indicator fura-2. Pregnenolone sulfate (5-250 microM) caused a concentration-dependent and reversible potentiation of the rise (up to approximately 800%) in [Ca2+]i induced by NMDA. In contrast, the steroid failed to alter basal (unstimulated) [Ca2+]i or to modify the rise in [Ca2+]i that occurs when hippocampal neurons are depolarized by high K+ in the presence of the NMDA receptor antagonist CPP. These data suggest that the previously reported excitatory properties of pregnenolone sulfate may be due, in part, to an augmentation of the action of glutamic acid at the NMDA receptor.
利用显微分光荧光测定法和钙离子敏感指示剂fura-2，在培养的胎鼠海马神经元中研究了神经活性甾体硫酸孕烯醇酮改变N-甲基-D-天冬氨酸（NMDA）受体介导的细胞内钙离子浓度升高（[Ca2+]i）的能力。硫酸孕烯醇酮（5 - 250微摩尔）导致由NMDA诱导的[Ca2+]i升高出现浓度依赖性且可逆的增强（高达约800%）。相反，该甾体未能改变基础（未刺激的）[Ca2+]i，也未能改变在NMDA受体拮抗剂CPP存在的情况下海马神经元被高钾去极化时出现的[Ca2+]i升高。这些数据表明，先前报道的硫酸孕烯醇酮的兴奋性特性可能部分归因于谷氨酸在NMDA受体处作用的增强。
