Zhu Gang, Okada Motohiro, Yoshida Shukuko, Hirose Shinichi, Kaneko Sunao
Department of Neuropsychiatry, Hirosaki University, Hirosaki 036-8562, Japan.
Neurosci Lett. 2004 May 27;362(3):244-8. doi: 10.1016/j.neulet.2004.03.031.
To clarify the striatal Ca2+-dependent monoaminergic exocytosis mechanisms, this study determined the effects of the Ca2+-induced Ca2+ releasing system (CICR), containing inositol-trisphosphate-receptor (IP3R) and ryanodine-receptor (RyR), on striatal releases of dopamine and its precursor, 3,4-dihydroxyphenylalanine (DOPA), using microdialysis. The basal dopamine release is regulated by IP3R but not by RyR, whereas basal DOPA release does not require CICR. The K+-evoked releases of DOPA and dopamine were enhanced by IP3R agonist, whereas RyR agonist reduced it. Additionally, inhibition of dopamine release induced by RyR hyperactivation was prevented by inhibition of L-type voltage-sensitive Ca2+-channel activity. These present results suggest that CICR-associated regulation of striatal releases of DOPA and dopamine is restrictive during the resting stage, whereas CICRs play an important role as a reserve mechanism of exocytosis of striatal DOPA and dopamine during the hyperexcitable stage.
为阐明纹状体中依赖钙离子的单胺能胞吐机制,本研究利用微透析技术,确定了包含肌醇三磷酸受体(IP3R)和兰尼碱受体(RyR)的钙离子诱导钙离子释放系统(CICR)对纹状体中多巴胺及其前体3,4-二羟基苯丙氨酸(DOPA)释放的影响。基础多巴胺释放受IP3R调节,而非RyR,而基础DOPA释放不需要CICR。IP3R激动剂增强了钾离子诱发的DOPA和多巴胺释放,而RyR激动剂则降低了这种释放。此外,抑制L型电压敏感性钙通道活性可防止RyR过度激活诱导的多巴胺释放。这些结果表明,在静息阶段,CICR相关的纹状体DOPA和多巴胺释放调节具有限制性,而在过度兴奋阶段,CICR作为纹状体DOPA和多巴胺胞吐的储备机制发挥重要作用。