Nagy J I, Vincent S R, Lehmann J, Fibiger H C, McGeer E G
Brain Res. 1978 Jun 30;149(2):431-41. doi: 10.1016/0006-8993(78)90485-7.
The selective destruction of neuronal perikarya via intracerebral injections of kainic acid was used to elucidate the cellular location of four neurotransmitter-related enzymes in the substantia nigra (SN). Two weeks after intranigral injections of kainic acid, dopamine-sensitive adenylate cyclase, glutamic acid decarboxylase (GAD), choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were measured in the SN. Histological examination of the SN, and a reduction of striatal tyrosine hydroxylase (TH) activity by 94%, confirmed the extensive loss of neuronal cell bodies in the SN. Dopamine stimulation of adenylate cyclase was not reduced in the lesioned SN, supporting the view that dendritically-released dopamine can regulate cyclic AMP synthesis in afferent terminals to these dendrites. Nigral GAD activity was significantly reduced by the lesions, suggesting that there are GAD-containing perikarya in the SN. CAT activity was not affected by the kainic injections, indicating the absence of cholinergic perikarya in the SN. Nigral AChE activity was significantly decreased after kainic injections, thus confirming the presence of AChE within the nigral perikarya. The results suggest that dopamine-sensitive adenylate cyclase and CAT are located within afferents to the SN, while GAD and AChE are found, to some extent at least, in neuronal soma of the SN. The differentail effects of kainic acid on these enzymes suggest that this compound may be a useful neurochemical tool with which to determine the cellular distribution of enzyme systems in the central nervous system.
通过脑内注射 kainic 酸选择性破坏神经元胞体，以阐明黑质（SN）中四种神经递质相关酶的细胞定位。在黑质内注射 kainic 酸两周后，检测黑质中的多巴胺敏感腺苷酸环化酶、谷氨酸脱羧酶（GAD）、胆碱乙酰转移酶（CAT）和乙酰胆碱酯酶（AChE）。对黑质的组织学检查以及纹状体酪氨酸羟化酶（TH）活性降低 94%，证实了黑质中神经元细胞体的大量丢失。损伤的黑质中多巴胺对腺苷酸环化酶的刺激未降低，支持树突释放的多巴胺可调节这些树突传入终末中环磷酸腺苷合成的观点。损伤使黑质 GAD 活性显著降低，提示黑质中存在含 GAD 的胞体。CAT 活性不受 kainic 酸注射影响，表明黑质中不存在胆碱能胞体。kainic 酸注射后黑质 AChE 活性显著降低，从而证实黑质胞体中存在 AChE。结果表明，多巴胺敏感腺苷酸环化酶和 CAT 位于黑质的传入纤维内，而 GAD 和 AChE 至少在一定程度上存在于黑质的神经元胞体中。kainic 酸对这些酶的不同作用表明，该化合物可能是一种有用的神经化学工具，可用于确定中枢神经系统中酶系统的细胞分布。
