Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype
Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype
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DOI：
10.1073/pnas.97.17.9579
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发表时间：
2000-08-15
影响因子：
11.1
通讯作者：
Taketo, MM
中科院分区：
文献类型：
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作者：
Matsui, M;Motomura, D;Taketo, MM
毒蕈碱型乙酰胆碱受体由五种不同的亚型组成，是药物开发的重要靶点。在外周，毒蕈碱型乙酰胆碱受体介导胆碱能信号到自主器官，但每个亚型的具体生理功能仍不清楚。在这里，我们已经构建和分析了突变小鼠缺乏M-3受体，并证明了这种亚型在唾液分泌，瞳孔收缩和膀胱逼尿肌收缩中起着关键作用。然而.消化和生殖器官中M-3介导的信号是不稳定的，可能是因为通过其他毒蕈碱乙酰胆碱受体亚型或其他介质的冗余机制。此外，我们发现只有男性有明显的尿潴留，这表明在排尿机制上有相当大的性别差异。因此，这种突变小鼠应该为研究外周胆碱能功能受影响的人类疾病提供有用的动物模型。
Muscarinic acetylchoIine receptors consist of five distinct subtypes and have been important targets for drug development. In the periphery, muscarinic acetylcholine receptors mediate cholinergic signals to autonomic organs, but specific physiological functions of each subtype remain poorly elucidated. Here, we have constructed and analyzed mutant mice lacking the M-3 receptor and have demonstrated that this subtype plays key roles in salivary secretion, pupillary constriction, and bladder detrusor contractions. However. M-3-mediated signals in digestive and reproductive organs are dispensable, likely because of redundant mechanisms through other muscarinic acetylcholine receptor subtypes or other mediators. In addition, we have found prominent urinary retention only in the male, which indicates a considerable sex difference in the micturition mechanism. Accordingly, this mutant mouse should provide a useful animal model for investigation of human diseases that are affected in the peripheral cholinergic functions.