Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, CF4 4XN, Cardiff, UK.
Amino Acids. 1995 Jun;8(2):159-69. doi: 10.1007/BF00806489.
The effects of the sulphonylurea activators of ATP-sensitive potassium channels (K(+) ATP), cromakalim and pinacidil, on the evoked-release of endogenous glutamate from superfused slices of rat cerebellum was examined. K(+)-stimulated release was Ca(2+)-dependent, whereas tetrapentylammonium (TPeA)-evoked release occurred both in the presence and absence of Ca(2+), but was significantly greater in Ca(2+)-free medium. The Ca(2+)-dependent TPeA and K(+)-evoked release of glutamate was inhibited by both cromakalim and pinacidil in a concentration-dependent fashion. However, although cromakalim markedly reduced Ca(2+)-independent TPeA-evoked release, pinacidil was ineffective. In addition, the vehicle for cromakalim, ethanol, markedly potentiated both Ca(2+)-dependent and -independent TPeA-evoked release, but not K(+)-evoked release. Despite a high concentration of sulphonylurea binding sites and a dense glutamatergic innervation, the concentrations of K(+) ATP channel activators required to inhibit stimulus-evoked release from the cerebellum are higher than those reported to inhibit glutamate release or reduce neuronal activity in other parts of the CNS.
我们考察了磺酰脲类三磷酸腺苷敏感性钾通道（K(+)ATP）激活剂克罗马林和吡那地尔对在体灌流的大鼠小脑薄片中内源性谷氨酸释放的诱发释放的影响。K(+)刺激释放依赖于 Ca(2+)，而四戊基铵（TPeA）诱发的释放既存在于 Ca(2+)存在的情况下，也存在于 Ca(2+)不存在的情况下，但在无 Ca(2+)的介质中显著增加。克罗马林和吡那地尔以浓度依赖性方式抑制 Ca(2+)依赖性 TPeA 和 K(+)诱发的谷氨酸释放。然而，尽管克罗马林显著降低了 Ca(2+)非依赖性 TPeA 诱发的释放，但吡那地尔却没有效果。此外，克罗马林的溶剂乙醇显著增强了 Ca(2+)依赖性和非依赖性 TPeA 诱发的释放，但不增强 K(+)诱发的释放。尽管磺酰脲类结合位点的浓度很高，且谷氨酸能神经支配密集，但抑制小脑刺激诱发释放所需的 K(+)ATP 通道激活剂的浓度高于那些报告抑制谷氨酸释放或降低中枢神经系统其他部位神经元活性的浓度。
