Cystometric findings in mice lacking muscarinic M2 or M3 receptors
Cystometric findings in mice lacking muscarinic M2 or M3 receptors
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DOI：
10.1097/01.ju.0000138054.77785.4a
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发表时间：
2004-12-01
影响因子：
6.6
通讯作者：
Andersson, KE
中科院分区：
文献类型：
--
作者：
Igawa, Y;Zhang, XY;Andersson, KE
目的：用缺乏M-3或M-2受体的小鼠和同窝WT对照，在体内研究毒蕈碱M-3和M-2受体对膀胱功能的生理重要性。材料与方法：未麻醉各组小鼠在给予阿托品（1 mg/kg(-1)）前后连续进行膀胱造影。结果：M-3基因敲除（KO）雄性小鼠排尿间隔时间较M-2基因敲除（KO）或WT雄性小鼠更长，排尿量和膀胱容量较大。雄性M-2 KO和WT小鼠的任何膀胱计量参数均无显著差异。雌性M-3 KO和M-2 KO小鼠排尿间隔较长，排尿量较WT大。阿托品对WT和M-2 KO小鼠的排尿效果有明显的抑制作用，但对M-3 KO小鼠的任何膀胱参数均无影响。结论：目前的结果证实M-3受体是引起膀胱收缩的主要毒蕈碱受体亚型，M-2受体的作用次要。在M-3 KO小鼠中发现的功能损伤比在WT小鼠中由阿托品急性阻断毒蕈碱受体引起的功能损伤要轻，这表明非胆碱能机制可以补偿M-3受体的慢性损失。
Purpose: The physiological importance of muscarinic M-3 and M-2 receptors for bladder function was investigated in vivo using mice lacking M-3 or M-2 receptors and littermate WT controls.Materials and Methods: Unanesthetized mice of each sex underwent continuous cystometry before and after administration of atropine (1 mg/kg(-1)).Results: Male M-3 knockout (KO) mice had longer voiding intervals, and larger micturition volumes and bladder capacity than M-2 KO or WT males. There was no significant difference in any cystometric parameters between male M-2 KO and WT mice. In females M-3 KO and M-2 KO mice had longer voiding intervals and larger micturition volumes than WT animals. Atropine had marked inhibitory effects on voiding efficacy in WT and M-2 KO mice but it had no effect on any cystometric parameters in M-3 KO mice.Conclusions: The current results confirm that M-3 receptor is the principal muscarinic receptor subtype responsible for bladder contraction and the role of M-2 receptors is of minor importance. Functional impairments found in M-3 KO mice were milder than those elicited by acute blockade of muscarinic receptors by atropine in WT mice, suggesting that noncholinergic mechanisms can compensate for a chronic loss of M-3 receptors.