Effects of Ca2+ channel antagonists on striatal dopamine and DOPA release, studied by in vivo microdialysis

被引:37
作者
Okada, M [1 ]
Wada, K [1 ]
Kiryu, K [1 ]
Kawata, Y [1 ]
Mizuno, K [1 ]
Kondo, T [1 ]
Tasaki, H [1 ]
Kaneko, S [1 ]
机构
[1] Hirosaki Univ, Sch Med, Dept Neuropsychiat, Hirosaki, Aomori 036, Japan
关键词
omega-agatoxin IVA; omega-conotoxin GVIA; omega-conotoxin MVIIC; 3,4-dihydroxyphenylalanine; dopamine; striatum;
D O I
10.1038/sj.bjp.0701675
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 To elucidate the mechanisms regulating the release of striatal dopamine and its precursor, 3,4-dihydroxyphenylalanine (DOPA), we determined the effects of various Ca2+ channel antagonists, an N-type Ca2+ channel antagonist, omega-conotoxin GVIA, a P-type Ca2+ channel antagonist, omega-agatoxin IVA, and a Q-type Ca2+ channel antagonist, omega-conotoxin MVIIC, on the basal and Ca2+- and K+-evoked release of striatal dopamine and DOPA, by use of in vivo microdialysis. 2 omega-Conotoxin GVIA strongly inhibited striatal basal dopamine release (IC50 = 0.48 nM), whereas this toxin only weakly modulated basal striatal DOPA release (IC50 = 9.55 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the basal striatal release of dopamine and DOPA. 3 omega-Conotoxin GVIA strongly inhibited Ca2+-evoked striatal dopamine release (IC50 = 0.40 nM), whereas Ca2+-evoked striatal DOPA release only was weakly modulated (IC50 = 10.51 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the Ca2+-evoked release of striatal dopamine and DOPA. 4 Both omega-agatoxin IVA and omega-conotoxin MVIIC inhibited the K+-evoked release of striatal dopamine (IC50 of omega-agatoxin IVA = 2.65 nM; IC50 of omega-conotoxin MVIIC = 12.54 nM) and DOPA (IC50 of omega-agatoxin IVA = 0.15 nM, IC50 of omega-conotoxin MVIIC = 3.05 nM), whereas omega-conotoxin GVIA had no effect on the K+-evoked release of striatal dopamine and DOPA. 5 An increase in the extracellular Ca2+ and K+ concentrations (Ca2+- and K+-evoked stimulation) did not affect tyrosine hydroxylase activity in vivo. 6 These findings suggest that striatal DOPA release is neurotransmitter-like and that, unlike the mechanisms of striatal dopaminergic transmission, this striatal DOPA transmission is at least partly regulated by voltage-sensitive Ca2+ channel.
引用
收藏
页码:805 / 814
页数:10
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