Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins.
Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins.
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发表时间：
1995-05
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通讯作者：
P. Wang;G. Luthin;M. Ruggieri
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作者：
P. Wang;G. Luthin;M. Ruggieri
毒蕈碱乙酰胆碱受体的激活主要负责膀胱排空。由于存在多种毒蕈碱受体亚型，我们希望表征膀胱中存在的毒蕈碱受体亚型，并最终将其功能归因于调节膀胱收缩性、神经递质释放以及该组织中其他胆碱能功能的亚型。虽然 m2 和 m3 亚型在从人、大鼠、兔和豚鼠膀胱膜中溶解后可以进行免疫沉淀，但 m1、m4 和 m5 亚型则不能。大鼠膀胱中的 m2:m3 比率为 9:1，但在所检查的其他物种中仅为 3:1。 m2 亚型的免疫沉淀与高亲和力激动剂结合位点的相对水平相关，该相对水平通过卡巴胆碱竞争[3H]N-甲基东莨菪碱的结合来测量或直接使用[3H]氧化震颤素-M来测量。在存在激动剂而非拮抗剂的情况下，GTP 结合蛋白可以使用抗受体抗体与 m2 或 m3 受体一起进行免疫沉淀。这些蛋白质是 m2 和 m3 受体亚型的 Gi 和 Gq/11 亚家族的成员。尽管m2受体在所有研究物种中占优势，但使用具有一定选择性的拮抗剂的Schild分析表明，药理学上定义的m3受体介导大鼠和兔膀胱条的收缩性。因此，乙酰胆碱通过 m3 受体亚型激活膀胱平滑肌，随后的收缩性可能由鸟嘌呤核苷酸结合蛋白（例如 Gi 和 Gq/11 亚家族）转导。
Activation of muscarinic acetylcholine receptors is primarily responsible for urinary bladder emptying. Because multiple subtypes of muscarinic receptors exist, we wished to characterize those present in bladder and ultimately to attribute function to those that regulate bladder contractility, neurotransmitter release and perhaps other cholinergic functions in this tissue. Although the m2 and m3 subtypes could be immunoprecipitated after solubilization from human, rat, rabbit and guinea pig bladder membranes, the m1, m4 and m5 subtypes could not. The m2:m3 ratio was 9:1 in rat bladder but was only 3:1 in the other species examined. Immunoprecipitation of the m2 subtype correlated with the relative levels of high-affinity agonist binding sites measured by competition of carbachol for [3H]N-methylscopolamine binding or measured directly using [3H]oxotremorine-M. In the presence of agonist, but not antagonist, GTP binding proteins could be immunoprecipitated in concert with the m2 or m3 receptors using anti-receptor antibodies. These proteins were members of the Gi and Gq/11 subfamilies for both the m2 and the m3 receptor subtypes. In spite of the preponderance of the m2 receptor in all species studied, Schild analysis using somewhat selective antagonists showed that the pharmacologically defined m3 receptor mediated contractility in strips of rat and rabbit bladder. Thus acetylcholine activates bladder smooth muscle via the m3 receptor subtype, and subsequent contractility may be transduced by guanine nucleotide binding proteins such as the Gi and Gq/11 subfamilies.