Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA.
J Clin Pharm Ther. 2009 Dec;34(6):623-9. doi: 10.1111/j.1365-2710.2009.01059.x.
Two reports published in the latter 1980s are generally given credit for being the first to announce the discovery of a new subtype of muscarinic acetylcholine receptor (mAChR), designated m5 or M5, and now officially M(5) (1). Both identifications were assigned using molecular biology techniques. Then - as now - no selective high-affinity ligands or toxins were available. In situ hybridization and reverse-transcriptase PCR have found M(5) AChR expression in brain to be distinct from that of the four other G protein-coupled mAChR subtypes and primarily localized to the substantia nigra, ventral tegmental area, hippocampus (CA1 and CA2 subfields), cerebral cortex (outermost layer) and striatum (caudate putamen). M(5) AChR brain region localization and involvement in the regulation of striatal dopamine release and in rewarding brain stimulation suggests a possible role for M(5) AChR as a target for novel therapy to treat excess hedonic drive, including drug abuse.
有两份发表于 20 世纪 80 年代后期的报告通常被认为是首次宣布发现一种新的毒蕈碱型乙酰胆碱受体（mAChR）亚型，命名为 m5 或 M5，现在正式称为 M(5)（1）。这两个鉴定都是使用分子生物学技术进行的。当时——就像现在一样——没有选择性的高亲和力配体或毒素可用。原位杂交和逆转录聚合酶链反应发现，M(5) AChR 在大脑中的表达与其他四种 G 蛋白偶联 mAChR 亚型不同，主要定位于黑质、腹侧被盖区、海马体（CA1 和 CA2 子场）、大脑皮层（最外层）和纹状体（尾状核苍白球）。M(5) AChR 在大脑区域的定位以及在调节纹状体多巴胺释放和奖赏性脑刺激中的作用表明，M(5) AChR 可能成为治疗过度享乐驱动的新型治疗靶点，包括药物滥用。
