Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, Seoul, Korea.
Korean J Anesthesiol. 2012 Mar;62(3):266-71. doi: 10.4097/kjae.2012.62.3.266. Epub 2012 Mar 21.
Clonidine has been shown to be a potent neuroprotectant by acting at α(2) receptors on glutamatergic neurons to inhibit the release of glutamate. The aim of this study is to investigate the effects of clonidine on the activity of EAAT3 that can regulate extracellular glutamate.
EAAT3 was expressed in the Xenopus oocytes. Using a two-electrode voltage clamp, membrane currents were recorded after application of 30 µM L-glutamate both in the presence and absence of various concentrations of clonidine. To determine the effects of clonidine on the K(m) and Vmax of EAAT3 and the reversibility of clonidine effects, membrane currents were recorded after the application of various concentrations of L-glutamate both in the presence and absence of 1.50 × 10(-7) M clonidine.
Clonidine reduced the EAAT3 responses to L-glutamate in a concentration-dependent manner. This inhibition was statistically significant at higher concentrations than at the clinically relevant range. Clonidine at 1.50 × 10(-7) M reduced the Vmax, but did not affect the K(m) of EAAT3 for L-glutamate.
These results suggest that the direct inhibition of EAAT3 activity is not related to the sedation effect of clonidine and that the clonidine-induced reduction of EAAT3 activity provides additional data for the possible involvement of glutamatergic hyperactivity in the proconvulsant effect of clonidine.
可乐定通过作用于谷氨酸能神经元上的 α(2)受体抑制谷氨酸的释放，已被证明具有很强的神经保护作用。本研究旨在探讨可乐定对 EAAT3 活性的影响，EAAT3 可调节细胞外谷氨酸。
EAAT3 在非洲爪蟾卵母细胞中表达。应用双电极电压钳技术，在存在和不存在各种浓度可乐定的情况下，应用 30µM L-谷氨酸后记录膜电流。为了确定可乐定对 EAAT3 的 K(m)和 Vmax 的影响以及可乐定作用的可逆性，在存在和不存在 1.50×10(-7)M 可乐定的情况下，应用各种浓度的 L-谷氨酸后记录膜电流。
可乐定以浓度依赖的方式降低 EAAT3 对 L-谷氨酸的反应。这种抑制在高于临床相关范围的浓度下具有统计学意义。1.50×10(-7)M 可乐定降低了 Vmax，但不影响 EAAT3 对 L-谷氨酸的 K(m)。
这些结果表明，EAAT3 活性的直接抑制与可乐定的镇静作用无关，而可乐定诱导的 EAAT3 活性降低为谷氨酸能过度活跃可能参与可乐定的促惊厥作用提供了额外的数据。
