通过体内微透析研究钙离子通道拮抗剂对纹状体多巴胺和多巴释放的影响。

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

作者信息

Okada M, Wada K, Kiryu K, Kawata Y, Mizuno K, Kondo T, Tasaki H, Kaneko S

机构信息

Department of Neuropsychiatry, School of Medicine, Hirosaki University, Japan.

出版信息

Br J Pharmacol. 1998 Mar;123(5):805-14. doi: 10.1038/sj.bjp.0701675.

DOI:10.1038/sj.bjp.0701675

PMID:9535007

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565231/

Abstract

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+ channels.

摘要

为阐明调节纹状体多巴胺及其前体3,4-二羟基苯丙氨酸（DOPA）释放的机制，我们利用体内微透析技术，测定了各种钙离子通道拮抗剂、N型钙离子通道拮抗剂ω-芋螺毒素GVIA、P型钙离子通道拮抗剂ω-阿加毒素IVA以及Q型钙离子通道拮抗剂ω-芋螺毒素MVIIC对纹状体多巴胺和DOPA基础释放以及钙离子和钾离子诱发释放的影响。2. ω-芋螺毒素GVIA强烈抑制纹状体基础多巴胺释放（IC50 = 0.48 nM），而该毒素对纹状体基础DOPA释放的调节作用较弱（IC50 = 9.55 nM）。ω-阿加毒素IVA和ω-芋螺毒素MVIIC均不影响纹状体多巴胺和DOPA的基础释放。3. ω-芋螺毒素GVIA强烈抑制钙离子诱发的纹状体多巴胺释放（IC50 = 0.40 nM），而钙离子诱发的纹状体DOPA释放仅受到较弱调节（IC50 = 10.51 nM）。ω-阿加毒素IVA和ω-芋螺毒素MVIIC均不影响钙离子诱发的纹状体多巴胺和DOPA释放。4. ω-阿加毒素IVA和ω-芋螺毒素MVIIC均抑制钾离子诱发的纹状体多巴胺释放（ω-阿加毒素IVA的IC50 = 2.65 nM；ω-芋螺毒素MVIIC的IC50 = 12.54 nM）和DOPA释放（ω-阿加毒素IVA的IC50 = 0.15 nM；ω-芋螺毒素MVIIC的IC50 = 3.05 nM），而ω-芋螺毒素GVIA对钾离子诱发的纹状体多巴胺和DOPA释放无影响。5. 细胞外钙离子和钾离子浓度升高（钙离子和钾离子诱发刺激）在体内不影响酪氨酸羟化酶活性。6. 这些发现表明，纹状体DOPA释放具有类似神经递质的特性，并且与纹状体多巴胺能传递机制不同，这种纹状体DOPA传递至少部分受电压敏感性钙离子通道调节。