Dopamine D1 receptor facilitation of depolarization-induced release of γ-amino-butyric acid in rat striatum is mediated by the cAMP/PKA pathway and involves P/Q-type calcium channels
Dopamine D1 receptor facilitation of depolarization-induced release of γ-amino-butyric acid in rat striatum is mediated by the cAMP/PKA pathway and involves P/Q-type calcium channels
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DOI：
10.1002/syn.20372
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发表时间：
2007-05-01
期刊：
影响因子：
2.3
通讯作者：
Young, J. M.
中科院分区：
文献类型：
--
作者：
Arias-Montano, J. -A.;Floran, B.;Young, J. M.
在控制运动运动中起重要作用的“直接”通路通过基底节的传递，明显地被同时激活的多巴胺D受体所促进。与此相一致的是，在多巴胺D-1受体激动剂M SKF 38393的存在下，利血平处理的大鼠纹状体脑片钙依赖的去极化诱导的[H-3]-GABA释放显著增加。用1 mM 8-溴环腺苷(BR-cAMP)模拟SKF 38393的作用，用蛋白激酶A(PKA)抑制剂H-89抑制，10 mU M H-89平均抑制92%+/-4%(n=3)。SKF-38393和BR-cAMP的作用不是相加的。组胺H-3受体激动剂Immepip(1mU·M)可使SKF-38393和BR-cAMP的兴奋作用完全消失。在SKF 38393存在下，去极化引起的[H-3]-GABA的释放不被L型钙通道阻断剂5 mU尼莫地平和N型通道选择性阻断剂0.3 mU芋螺毒素MVIIA显著抑制。然而，用P/Q型通道阻滞剂M omega-agatoxin TK预孵育脑片，然后洗涤，然后换成含有SKF 38393的去极化介质，可显著抑制刺激的[H-3]-氨基丁酸的释放，平均为+/-4%(n=3)。这些观察结果表明，多巴胺D激动剂易化去极化诱导的GABA从纹状体终末释放，是由cAMP/PKA途径介导的，主要涉及P/Q型钙通道。
Transmission in the "direct" pathway through the basal ganglia, which has an important role in the control of motor movement, is markedly facilitated by the concurrent activation of dopamine D, receptors. Consistent with this, Ca2+-dependent, depolarization-induced release of [H-3]-GABA from striatal slices from rats pretreated with reserpine was greatly increased in the presence of 1 mu M SKF 38393, a dopamine D-1-like receptor agonist. The effect of SKF 38393 was mimicked by 1 mM 8-bromo-cyclic AMP (Br-cAMP) and inhibited by the protein kinase A (PKA) inhibitor H-89, mean inhibition 92% +/- 4% with 10 mu M H-89 (n = 3). The effects of SKF 38393 and Br-cAMP were not additive. The stimulatory effects of SKF 38393 and Br-cAMP were practically abolished in the presence of the histamine H-3 receptor agonist immepip (1 mu M). The depolarization-induced release of [H-3]-GABA in the presence of SKF 38393 was not significantly inhibited by 5 mu M nimodipine, an L-type Ca2+ channel blocker, or by 0.3 mu M omega-conotoxin MVIIA, a selective blocker of N-type channels. However, preincubation of the slices with 0.95 mu M omega-agatoxin TK, a P/Q-type channel blocker, followed by washing before changing to a depolarizing medium containing SKF 38393, resulted in a marked inhibition of the stimulated release of [H-3]-GABA, mean 68% +/- 4% (n = 3). These observations provide evidence that dopamine D, agonist facilitation of the depolarization-induced release of GABA from striatal terminals is mediated by the cAMP/PKA pathway and involves mainly P/Q-type Ca2+ channels.