Sanvarinda Y, Phivthongngam L, Govitrapong P
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Neurochem Int. 1998 Aug;33(2):187-93. doi: 10.1016/s0197-0186(98)00005-9.
Dopamine deficiency syndrome is known to cause cholinergic hyperactivity. Therefore, it was hypothesized that the said phenomenon may be due to enhanced cholinergic receptor functions. In the present study we examined the changes in striatal dopaminergic and cholinergic receptors in unilateral substantia nigra lesioned rats that showed vigorous ipsilateral rotation (total turns > 300) in response to apomorphine (1 mg kg(-1) ip). [3H] Spiperone ([3H]-SP) and [3H]-quinuclidinyl benzilate ([3H]-QNB) bindings were performed in the striata of the lesioned animals. There was no significant difference in the dissociation equilibrium constant values (Kd) between the lesioned and non-lesioned sides. However, a significant difference in the maximum receptor density (Bmax) of both [3H]-SP and [3H]-QNB bindings was observed between the lesioned and non-lesioned sides. The Bmax of [3H]-SP binding was significantly decreased on the lesioned side, whereas the Bmax of the [3H]-QNB binding was significantly increased. These results support the hypothesis that deficiencies of the dopaminergic system cause overactivity of the cholinergic system in the striatum.
已知多巴胺缺乏综合征会导致胆碱能功能亢进。因此,有人提出上述现象可能是由于胆碱能受体功能增强所致。在本研究中,我们检测了单侧黑质损伤大鼠纹状体中多巴胺能和胆碱能受体的变化,这些大鼠对阿扑吗啡(1 mg kg⁻¹腹腔注射)表现出强烈的同侧旋转(总旋转次数>300)。在损伤动物的纹状体中进行了[³H]司哌罗 ([³H]-SP) 和[³H]喹核醇基苯甲酸酯 ([³H]-QNB) 结合实验。损伤侧与未损伤侧之间的解离平衡常数 (Kd) 值没有显著差异。然而,在损伤侧与未损伤侧之间观察到[³H]-SP和[³H]-QNB结合的最大受体密度 (Bmax) 存在显著差异。[³H]-SP结合的Bmax在损伤侧显著降低,而[³H]-QNB结合的Bmax显著增加。这些结果支持了多巴胺能系统缺陷导致纹状体胆碱能系统过度活跃这一假说。