Maneuf Y P, Duty S, Hille C J, Crossman A R, Brotchie J M
Division of Neuroscience, School of Biological Sciences, University of Manchester, United Kingdom.
Exp Neurol. 1996 May;139(1):12-6. doi: 10.1006/exnr.1996.0075.
An ATP-sensitive potassium channel (KATP) is known to modulate insulin release from pancreatic beta cells. It has been proposed that potassium channels related to KATP in the nervous system might similarly modulate neurotransmitter release. We have therefore investigated the effects of KATP opening agents on GABA release in the globus pallidus. Diazoxide and cromakalim decreased the K(+)-evoked release of [3H]GABA from pallidal slices. The maximum inhibition observed for diazoxide (59%) and cromakalim (66%) was achieved at a concentration of 100 microM. The effects of both cromakalim and diazoxide were significantly antagonized by the concurrent application of the sulfonylurea glibenclamide (100 microM). Intrapallidal injections of diazoxide in the reserpine-treated rat model of Parkinson's disease reduced akinesia in a dose-dependent manner. These data suggest that manipulation of neuronal potassium channels with pharmacological properties similar to KATP may prove useful in the treatment of Parkinson's disease.
已知一种ATP敏感性钾通道（KATP）可调节胰腺β细胞释放胰岛素。有人提出，神经系统中与KATP相关的钾通道可能同样调节神经递质的释放。因此，我们研究了KATP开放剂对苍白球中γ-氨基丁酸（GABA）释放的影响。二氮嗪和克罗卡林可降低K⁺诱发的苍白球切片中[³H]GABA的释放。二氮嗪（59%）和克罗卡林（66%）在100微摩尔浓度时达到最大抑制作用。同时应用磺脲类药物格列本脲（100微摩尔）可显著拮抗克罗卡林和二氮嗪的作用。在利血平处理的帕金森病大鼠模型中，向苍白球内注射二氮嗪可剂量依赖性地减轻运动不能。这些数据表明，利用具有与KATP相似药理学特性的神经元钾通道进行调控，可能对帕金森病的治疗有用。
