EXPRESSION OF MUSCARINIC ACETYLCHOLINE AND DOPAMINE RECEPTOR MESSENGER-RNAS IN RAT BASAL GANGLIA

EXPRESSION OF MUSCARINIC ACETYLCHOLINE AND DOPAMINE RECEPTOR MESSENGER-RNAS IN RAT BASAL GANGLIA
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DOI:
10.1073/pnas.87.18.7050
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发表时间:
1990-09-01
影响因子:
11.1
通讯作者:
BRANN, MR
BRANN, MR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
WEINER, DM;LEVEY, AI;BRANN, MR

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在基底神经节内,乙酰胆碱和多巴胺在运动功能的锥体外系控制中发挥核心作用。这些神经递质的生理效应是由多种受体亚型介导的,其中几种现已被克隆。毒蕈碱乙酰胆碱受体由五个基因(m1-m5)编码,在两种已知的多巴胺受体亚型(D1和D2)中,D2受体基因已被表征。为了深入了解这些受体亚型的生理作用,我们制备了寡核苷酸探针,通过原位杂交组织化学在大鼠纹状体和黑质内定位受体亚型mRNA。在纹状体内,检测到三种毒蕈碱(m1,m2,m4)受体mRNA和D2受体mRNA。m1 mRNA在大多数神经元中表达(> 80%); m2 mRNA在非常大和罕见的神经元中表达; m4和D2 mRNA在40-50%的神经元中表达,其中三分之一表达两种mRNA。在黑质内,pars延髓,只有m5和D2的mRNA被检测到,大多数神经元表达这两种mRNA。这些数据为介导毒蕈碱和多巴胺能药物对基底神经节功能的不同作用的受体亚型的身份提供了解剖学证据。
Within the basal ganglia, acetylcholine and dopamine play a central role in the extrapyramidal control of motor function. The physiologic effects of these neurotransmitters are mediated by a diversity of receptor subtypes, several of which have now been cloned. Muscaranic acetylcholine receptors are encoded by five genes (m1-m5), and of the two know dopamine receptor subtypes (D1 and D2) the D2 receptor gene has been characterized. To gain insight into the physiological roles of each of these receptor subtypes, we prepared oligodeoxynucleotide probes to localize receptor subtype mRNAs within the rat striatum and substantia nigra by in situ hybridization histochemistry. Within the striatum, three muscarinic (m1, m2, m4) receptor mRNAs and the D2 receptor mRNA were detected. The m1 mRNA was expressed in most neurons (> 80%); the m2 mRNA, in neurons which were both very large and rare; and the m4 and D2 mRNAs, in 40-50% of the neurons, one-third of which express both mRNAs. Within the substantia nigra, pars compacta, only the m5 and D2 mRNAs were detected, and most neurons expressed both mRNAs. These data provide anatomical evidence for the identity of the receptor subtypes which mediate the diverse effects of muscarinic and dopaminergic drugs on basal ganglia function.