Narumi S, Nagai Y, Nagawa Y
Nihon Yakurigaku Zasshi. 1979 Apr 20;75(3):239-50. doi: 10.1254/fpj.75.239.
The enhancing effect of TRH on dopamine(DA) release from rat striatal slices was investigated in relation to Ca2+ and cholinergic mechanisms. TRH(10(-5)--10(-3) M) facilitated concentration dependently the uptake of 14C-DA by rat striatal slices, while methamphetamine (10(-6)--10(-4)M) exhibited a considerable inhibitory effect. TRH (10(-7)--10(--3)M) alone did not increase the DA release into the incubation medium, but it clearly enhanced the DA release in the concomitant presence of desipramine (5 x 10(-5)M). In the superfusion study, TRH (10(-5)--10(-3)M), methamphetamine (10(-6)--10(-4)M) and KCl (2.5--5.0 x 10(-2)M) enhanced the DA release into the perfusion fluid. The DA releasing effect of TRH was completely blocked by cholinergic blockers (scopolamine, hexamethonium and hemicholinium), Ca2+ chelator(EGTA), Ca2+ antagonist(CoCl2) and Ca2+ influx blocker(D-600) or by the removal of Ca2+ from the medium. The methamphetamine-enhanced DA release, however, was not modified by the above treatments except for a partial decline produced by EGTA coupled with the removal of Ca2+. TRH(10(-4)M) also facilitated the uptake of norepinephrine (NE) by rat cerebral cortex slices, but methamphetamine (10-(6)--10(-4)M) exhibited a considerable inhibitory effect. In the superfusion study, TRH (10(-5)--10(-4)M) and methamphetamine (10(-7)--10(-4)M) enhanced the NE release into the perfusion fluid. Therefore, it can be concluded that TRH facilitated the DA release from rat striatal slices by mediating through a cholinergic mechanism and enhancing the influx of Ca2+.
研究了促甲状腺激素释放激素(TRH)对大鼠纹状体切片中多巴胺(DA)释放的增强作用及其与Ca2+和胆碱能机制的关系。TRH(10(-5) - 10(-3)M)浓度依赖性地促进大鼠纹状体切片对14C - DA的摄取,而甲基苯丙胺(10(-6) - 10(-4)M)则表现出相当大的抑制作用。单独使用TRH(10(-7) - 10(-3)M)不会增加孵育培养基中DA的释放,但在存在地昔帕明(5×10(-5)M)的情况下,它能明显增强DA的释放。在灌流研究中,TRH(10(-5) - 10(-3)M)、甲基苯丙胺(10(-6) - 10(-4)M)和氯化钾(2.5 - 5.0×10(-2)M)均可增强灌注液中DA的释放。TRH的DA释放作用被胆碱能阻滞剂(东莨菪碱、六甲铵和半胱胺)、Ca2+螯合剂(乙二醇双四乙酸,EGTA)、Ca2+拮抗剂(氯化钴,CoCl2)和Ca2+内流阻滞剂(D - 600)完全阻断,或通过从培养基中去除Ca2+而阻断。然而,上述处理对甲基苯丙胺增强的DA释放没有影响,只有EGTA与去除Ca2+联合使用时会使其部分下降。TRH(10(-4)M)也促进大鼠大脑皮层切片对去甲肾上腺素(NE)的摄取,但甲基苯丙胺(10(-6) - 10(-4)M)表现出相当大的抑制作用。在灌流研究中,TRH(10(-5) - 10(-4)M)和甲基苯丙胺(10(-7) - 10(-4)M)增强灌注液中NE的释放。因此,可以得出结论,TRH通过胆碱能机制介导并增强Ca2+内流,促进大鼠纹状体切片中DA的释放。