Hársing L G, Vizi E S
Pol J Pharmacol Pharm. 1985 May-Jun;37(3):383-96.
The involvement of heterogeneous dopamine (DA) receptors in the regulation of striatal cholinergic neurotransmission was investigated by measuring the release of acetylcholine (ACh) from isolated striatum of the rat. The DA agonists apomorphine (3.7 X 10(-7)-7.4 X 10(-4) mol/l) and piribedil (3.3 X 10(-6)-9.9 X 10(-5) mol/l) exerted a biphasic action: in low concentrations they enhanced, while in high concentrations they inhibited, the ouabain-induced release of ACh. The enhancement of ACh release elicited by low concentrations of DA agonists was reversed by a noncataleptogenic dose of pimozide. 6-hydroxydopamine (6-OHDA) pretreatment also prevented the stimulatory action of apomorphine or piribedil on ACh release. In 6-OHDA pretreated striatum, apomorphine caused a biphasic inhibition of ACh release in a concentration dependent manner. DPI (3,4-dihydroxyphenylamino/-2-imidazoline, 2.5 X 10(-5)-2.5 X 10(-4) mol/l) increased the release of ACh in a monophasic manner and did not induce inhibition of transmitter output in 6-OHDA pretreated striatum. Pretreatment of rats with increasing doses of haloperidol or pimozide (0.037-15 mg/kg) exerted a biphasic action on striatal ACh release; low doses decreased and high doses enhanced the transmitter output and the elevation was accompanied by the appearance of catalepsy. From these experiments it is concluded that multiple DA receptors are involved in the regulation of striatal cholinergic neurotransmission. Among these, the presynaptic DA autoreceptors located on nigrostriatal nerve endings are the most sensitive to both agonists and antagonists. DA receptors located on cholinergic interneurons of the striatum, which are postsynaptic in relation to nigrostriatal neurons, possess high and low affinity to apomorphine. Stimulation of DA autoreceptors enhances, while that of postsynaptic DA receptors leads to inhibition of ACh release.
通过测量大鼠离体纹状体中乙酰胆碱（ACh）的释放，研究了异质性多巴胺（DA）受体在纹状体胆碱能神经传递调节中的作用。DA激动剂阿扑吗啡（3.7×10⁻⁷ - 7.4×10⁻⁴mol/L）和吡贝地尔（3.3×10⁻⁶ - 9.9×10⁻⁵mol/L）发挥双相作用：低浓度时增强，高浓度时抑制哇巴因诱导的ACh释放。低浓度DA激动剂引起的ACh释放增强可被非致僵剂量的匹莫齐特逆转。6-羟基多巴胺（6-OHDA）预处理也可阻止阿扑吗啡或吡贝地尔对ACh释放的刺激作用。在6-OHDA预处理的纹状体中，阿扑吗啡以浓度依赖性方式对ACh释放产生双相抑制。DPI（3,4-二羟基苯氨基/-2-咪唑啉，2.5×10⁻⁵ - 2.5×10⁻⁴mol/L）以单相方式增加ACh释放，且在6-OHDA预处理的纹状体中不诱导递质释放抑制。用递增剂量的氟哌啶醇或匹莫齐特（0.037 - 15mg/kg）预处理大鼠对纹状体ACh释放发挥双相作用；低剂量降低，高剂量增强递质释放，且释放增加伴随着僵住症的出现。从这些实验得出结论，多种DA受体参与纹状体胆碱能神经传递的调节。其中，位于黑质纹状体神经末梢的突触前DA自身受体对激动剂和拮抗剂最为敏感。位于纹状体胆碱能中间神经元上的DA受体，相对于黑质纹状体神经元是突触后受体，对阿扑吗啡具有高亲和力和低亲和力。刺激DA自身受体增强，而刺激突触后DA受体导致ACh释放抑制。
