Inazu M, Kubota N, Takeda H, Oguchi K, Koizumi M, Kimura S, Matsumiya T
Department of Pharmacology and Intractable Diseases Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Neurochem Int. 2001 Sep;39(3):253-60. doi: 10.1016/s0197-0186(01)00015-8.
We examined the properties of voltage-dependent Ca(2+) channels (VDCCs) mediating 1-methyl-4-phenylpyridinium (MPP(+))-evoked [3H]DA release from rat striatal slices. In some cases, the Ca(2+)-independent efflux of neurotransmitters is mediated by the high-affinity neurotransmitter-uptake systems. To determine whether such a mechanism might be involved in MPP(+)-evoked [3H]DA release. MPP(+) (1,10 and 100 microM) evoked the release of [3H]DA from rat striatal slices in a concentration-dependent manner. In the absence of Ca(2+), MPP(+) (10 and 100 microM)-evoked [3H]DA release was significantly decreased to approximately 50% of control (a physiological concentration of Ca(2+)). In the presence of Ca(2+), nomifensine (0.1,1 and 10 microM) dose-dependently and significantly inhibited the MPP(+)-evoked release of [3H]DA. Nomifensine (1 and 10 microM) also dose-dependently and significantly inhibited the MPP(+)-evoked release of [3H]DA under Ca(2+)-free conditions. MPP(+)-evoked [3H]DA release was partly inhibited by nicardipine (1 and 10 microM), an L-type Ca(2+) channel blocker. On the other hand, the N-type Ca(2+) channel blocker omega-conotoxin-GVIA (omega-CTx-GVIA) (1 and 3 microM) did not affect this release. omega-agatoxin-IVA (omega-Aga-IVA) at low concentrations (0.1 microM), which are sufficient to block P-type Ca(2+) channels alone, also had no effect. On the other hand, MPP(+)-evoked [3H]DA release was significantly decreased by high concentrations of omega-Aga-IVA (0.3 microM) that would inhibit Q-type Ca(2+) channels. In addition, application of the Q-type Ca(2+) channel blocker omega-conotoxin-MVIIC (omega-CTx-MVIIC) (0.3 and 1 microM) also significantly inhibited MPP(+)-evoked [3H]DA release. These results suggest that MPP(+)-evoked [3H]DA release from rat striatal slices is largely mediated by Q-type Ca(2+) channels, and the Ca(2+)-independent component is mediated by reversal of the DA transport system.
我们研究了介导1-甲基-4-苯基吡啶鎓（MPP⁺）诱发大鼠纹状体切片释放[³H]多巴胺（[³H]DA）的电压依赖性钙通道（VDCCs）的特性。在某些情况下，神经递质的钙非依赖性外流由高亲和力神经递质摄取系统介导。为了确定这种机制是否可能参与MPP⁺诱发的[³H]DA释放。MPP⁺（1、10和100微摩尔）以浓度依赖性方式诱发大鼠纹状体切片释放[³H]DA。在无钙情况下，MPP⁺（10和100微摩尔）诱发的[³H]DA释放显著降低至对照（生理浓度的钙）的约50%。在有钙存在时，诺米芬辛（0.1、1和10微摩尔）剂量依赖性且显著抑制MPP⁺诱发的[³H]DA释放。诺米芬辛（1和10微摩尔）在无钙条件下也剂量依赖性且显著抑制MPP⁺诱发的[³H]DA释放。MPP⁺诱发的[³H]DA释放部分受到L型钙通道阻滞剂尼卡地平（1和10微摩尔）的抑制。另一方面，N型钙通道阻滞剂ω-芋螺毒素-GVIA（ω-CTx-GVIA）（1和3微摩尔）对这种释放没有影响。低浓度（0.1微摩尔）的ω-阿加毒素-IVA（ω-Aga-IVA），其单独足以阻断P型钙通道，也没有作用。另一方面，高浓度（0.3微摩尔）的ω-Aga-IVA会抑制Q型钙通道，从而显著降低MPP⁺诱发的[³H]DA释放。此外，应用Q型钙通道阻滞剂ω-芋螺毒素-MVIIC（ω-CTx-MVIIC）（0.3和1微摩尔）也显著抑制MPP⁺诱发的[³H]DA释放。这些结果表明，MPP⁺诱发大鼠纹状体切片释放[³H]DA主要由Q型钙通道介导，且钙非依赖性成分由多巴胺转运系统的反向转运介导。
