Pharmacological discrimination of protein kinase associated exocytosis mechanisms between dopamine and 3,4-dihydroxyphenylalanine in rat striatum using in vivo microdialysis
Pharmacological discrimination of protein kinase associated exocytosis mechanisms between dopamine and 3,4-dihydroxyphenylalanine in rat striatum using in vivo microdialysis
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DOI：
10.1016/j.neulet.2004.03.054
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发表时间：
2004-06
影响因子：
2.5
通讯作者：
G. Zhu;M. Okada;S. Yoshida;S. Hirose;S. Kaneko
中科院分区：
文献类型：
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作者：
G. Zhu;M. Okada;S. Yoshida;S. Hirose;S. Kaneko
为探讨多巴胺及其前体3，4-二羟基苯丙氨酸（DOPA）的胞吐机制，我们采用微透析技术研究了蛋白激酶、环腺苷酸依赖性蛋白激酶（PKA）、钙磷脂依赖性蛋白激酶（PKC）和钙调素依赖性蛋白激酶II（CaMK-II）对大鼠纹状体多巴胺和DOPA释放的影响。PKC和CaMK-II抑制剂主要减少基础DOPA和多巴胺释放，PKA抑制剂减弱。PKC和CaMK-II抑制剂可降低Ca 2+诱发的释放，但PKA抑制剂不降低。PKA和CaMK-II抑制剂主要抑制K+诱发的（20 min）释放，PKC抑制剂则减弱。持续K+诱发（120分钟）释放的多巴和多巴胺的CaMK-Ⅱ抑制剂减少，但不是由PKC或PKA。PKA和CaMK-II抑制剂可明显抑制DOPA的蓄积，而PKC抑制剂的抑制作用较弱。因此，本研究表明，纹状体多巴胞吐是由类似的蛋白激酶相关的多巴胺胞吐机制。
To explore the exocytosis mechanism of dopamine and its precursor, 3,4-dihydroxyphenylalanine (DOPA), we determined the effects of protein-kinase, cyclic-AMP-dependent protein-kinase (PKA), Ca2+-phospholipid-dependent protein-kinase (PKC) and Ca2+-calmodulin-dependent protein-kinase II (CaMK-II) on dopamine and DOPA releases in rat striatum using microdialysis. Basal DOPA and dopamine releases were reduced by PKC and CaMK-II inhibitors predominantly, and PKA inhibitor weakly. Ca2+-evoked releases were reduced by PKC and CaMK-II inhibitors, but not by PKA inhibitor. K+-evoked (20 min) releases were reduced by PKA and CaMK-II inhibitors predominantly, and PKC inhibitor weakly. Sustained K+-evoked (120 min) releases of DOPA and dopamine were reduced by CaMK-II inhibitor, but not by PKC or PKA. DOPA accumulation was reduced by PKA and CaMK-II inhibitors strongly, and PKC inhibitor weakly. Therefore, the present study demonstrates that striatal DOPA exocytosis is regulated by a similar protein kinase-associated exocytosis mechanism as that of dopamine.