Novel Insights into M-3 Muscarinic Acetylcholine Receptor Physiology and Structure

作者：Kruse Andrew C; Li Jianhua; Hu Jianxin; Kobilka Brian K; Wess Juergen^*

来源：Journal of Molecular Neuroscience, 2014, 53(3): 316-323.

DOI：10.1007/s12031-013-0127-0

• Muscarinic acetylcholine receptor
• G protein-coupled receptor
• X-ray structure
• Mutant mouse models
• Muscarinic receptor physiology

Recent studies with M-3 muscarinic acetylcholine receptor (M3R) mutant mice suggest that drugs selectively targeting this receptor subtype may prove useful for the treatment of various pathophysiological conditions. Moreover, the use of M3R-based designer G protein-coupled receptors (GPCRs) has provided novel insights into how G(q)-coupled GPCRs can modulate whole-body glucose homeostasis by acting on specific peripheral cell types. More recently, we succeeded in using X-ray crystallography to determine the structure of the M3R bound to the bronchodilating drug tiotropium, a muscarinic antagonist (inverse agonist). This new structural information should facilitate the development of orthosteric or allosteric M3R-selective drugs that are predicted to have considerable therapeutic potential.

• 出版日期2014-7