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Transmitter-like release of endogenous DOPA and regulatory actions of L-DOPA on the release of dopamine via presynaptic receptors in rat striatal and hypothalamic slices.

内源性多巴的递质样释放以及左旋多巴通过大鼠纹状体和下丘脑切片中突触前受体对多巴胺释放的调节作用。

基本信息

批准号：
61480119
负责人：
MISY Yoshimi
金额：
$ 3.84万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

DOPA, a precursor of dopamine (DA), has been generally accepted to act through its conversion to DA by DOPA-decarboxylase. However, depolarization released endogenous DOPA from superfused slices of rat striata. We compared the characteristics of the DOPA release with those of DA and also studied actions of exogenously applied DOPA on the release of DA and norepinephrine (NE).1. Electrical field stimulation with biphasic impulses (2 Hz) released DOPA and DA via a terodo toxin-sensitive and Ca^<2+>-dependent process. High K^+ 715 mM) also released DOPA and DA via a Ca^<2+> dependent process. In slices superfused with ^3H-tyrosine (1 <micro>M)-containing medium, high K^+ (15 and 60 mM) released DOPA and DA with a concentration-dependent decrease in tyrosine hydroxylase activity, ^3H-H_2O formation, followed by a concentration-dependent increase after the release of DA ended. DOPA appears to be released by an excitation-secretion coupling process.2. In striatal alices, DOPA 30 nM facilitated the evoked release of DA without increases in the sponyaneous release and tissue content of DA. In the presence of NSD-1055, a DOPA-decarboxylase inhi bitor, DOPA 10 nM to 1 <micro>M produces biphasic actions on the evoked release of DA, facilitation at 30 nM via presynaptic <beta>-adrenoceptors and inhibition at 1 <micrn>M via presynaptic DA receptor Similar biphasic actions of DOPA on the release of DA and NE were also seen in rat hypothalamic slices.A transmitter-like release of DOPA was seen in rat striatal slices. Biphasic regulatory actions of DOPA itself on the release of DA and NE seen in rat striatal and hypothalamic slices. These findings support a working hypothesis that DOPA plays a role as a neuroactive substance in these brain regions.

多巴是多巴胺（DA）的前体，一般认为是通过多巴脱羧酶将其转化为DA发挥作用。然而，去极化释放内源性多巴从灌流切片的大鼠纹状体。比较了多巴和多巴胺的释放特性，并研究了外源性多巴对多巴胺和去甲肾上腺素（NE）释放的影响.双相脉冲电场刺激（2 Hz）通过一个对terodo毒素敏感且依赖Ca^2+的过程释放多巴和多巴胺。高K^+（715 mM）也通过Ca^<2+>依赖性过程释放多巴和DA。在灌流含^3H-酪氨酸（1 M）的培养基的脑片中<micro>，高K^+（15和60 mM）释放多巴和DA，酪氨酸羟化酶活性和^3 H-H_2 O形成呈浓度依赖性降低，DA释放结束后呈浓度依赖性增加。多巴的释放似乎是通过兴奋-分泌偶联过程进行的。在纹状体，DOPA 30 nM促进DA的诱发释放，但不增加DA的自发释放和组织含量。在DOPA脱羧酶抑制剂NSD-1055存在下，DOPA 10 nM至1 <micro>M对DA的诱发释放产生双相作用，30 nM通过突触<beta>前肾上腺素受体促进，1 <micrn>M通过突触前DA受体抑制。在大鼠下丘脑脑片也观察到DOPA对DA和NE释放的类似双相作用。在大鼠纹状体切片中观察到DOPA的类似释放。多巴本身对大鼠纹状体和下丘脑脑片DA和NE释放的双相调节作用。这些发现支持了一个工作假设，即多巴在这些大脑区域中起着神经活性物质的作用。