Smith S S
Department of Anatomy, Hahnemann University, Philadelphia, PA 19102.
Neuroscience. 1991;42(2):309-20. doi: 10.1016/0306-4522(91)90377-z.
We have previously shown that the sex steroid progesterone plays a modulatory role in amino acid physiology by suppressing excitatory responses of cerebellar Purkinje cells to glutamate and augmenting inhibitory responses of these neurons to GABA. In the present study using the rat, progesterone effects on neuronal responses to the specific excitatory amino acid agonists quisqualate, kainate and N-methyl-D-aspartate were tested using iontophoretic, extracellular single unit recording techniques. In addition, the effect of systemic administration of progesterone on quisqualate-evoked excitation was evaluated in the presence of the GABAA blocker bicuculline. Progesterone consistently attenuated excitatory neuronal responses to local application of all three excitatory amino acids by 40-51%, but exerted variable effects on combined administration of quisqualate and N-methyl-D-aspartate which were dependent on temporal and dose-related factors. Progesterone-induced attenuation of the quisqualate response was found to be mediated primarily by a non-N-methyl-D-aspartate receptor. In addition, bicuculline application did not block progesterone effects on quisqualate excitation, suggesting that the observed steroidal modulation of excitatory amino acid function is not secondary to progesterone-induced potentiation of GABA inhibition.
我们之前已经表明，性类固醇孕酮通过抑制小脑浦肯野细胞对谷氨酸的兴奋性反应并增强这些神经元对GABA的抑制性反应，在氨基酸生理学中发挥调节作用。在本研究中，使用大鼠，采用离子电泳、细胞外单单位记录技术测试了孕酮对神经元对特定兴奋性氨基酸激动剂quisqualate、海人藻酸和N-甲基-D-天冬氨酸反应的影响。此外，在存在GABAA阻断剂荷包牡丹碱的情况下，评估了全身给予孕酮对quisqualate诱发兴奋的影响。孕酮持续使对局部应用的所有三种兴奋性氨基酸的兴奋性神经元反应减弱40%-51%，但对quisqualate和N-甲基-D-天冬氨酸联合给药产生的影响则因时间和剂量相关因素而异。发现孕酮诱导的quisqualate反应减弱主要由非N-甲基-D-天冬氨酸受体介导。此外，应用荷包牡丹碱并未阻断孕酮对quisqualate兴奋的影响，这表明观察到的类固醇对兴奋性氨基酸功能的调节并非继发于孕酮诱导的GABA抑制增强。
