Identification of three muscarinic receptor subtypes in rat lung using binding studies with selective antagonists.
Identification of three muscarinic receptor subtypes in rat lung using binding studies with selective antagonists.
复制标题
使用选择性拮抗剂的结合研究鉴定大鼠肺中的三种毒蕈碱受体亚型。
DOI：
10.1016/0024-3205(90)90572-9
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发表时间：
1990
期刊：
影响因子：
6.1
通讯作者：
el-Fakahany,EE
中科院分区：
文献类型：
--
作者：
Fryer,AD;el-Fakahany,EE
在使用选择性拮抗剂哌仑西平、AF-DX 116 和六氢硅拉非尼醇 (HHSiD) 进行的 [3H]苯苯甲酸奎宁环酯 ([3H]QNB) 竞争结合实验中，发现大鼠中央和外周肺中毒蕈碱受体群体的异质性。哌仑西平以低亲和力从中央气道制备物中取代[3H]QNB，表明气管和支气管中不存在M1受体。中央气道中的毒蕈碱受体由 M2 和 M3 受体组成，因为 AF-DX 116（一种 M2 选择性拮抗剂）以高亲和力与 70% 的可用位点结合，而 HHSiD（一种 M3 选择性拮抗剂）以高亲和力与其余结合位点结合。在外周肺中，哌仑西平以高亲和力结合至 14% 的受体群，AF-DX 116 以高亲和力结合至 79% 的结合位点，而 HHSiD 以高亲和力结合至 18% 的结合位点。使用M1受体配体[3H]替仑西平证实M1受体存在于外周气道中，但不存在于中央气道中。 [3H]替仑西平与大鼠外周肺匀浆中8%的[3H]QNB标记结合位点表现出特异性饱和结合，而在大鼠气管或心脏匀浆中没有可检测到的特异性结合。这里提出的结果表明，大鼠肺部存在三种毒蕈碱受体亚型，并且不同亚型在肺内的分布不同。在整个气道中，主要的毒蕈碱受体亚型是 M2。在气管和支气管中，剩余的受体是M3，而在外周肺中，剩余的受体是M1和M3。
Heterogeneity of the muscarinic receptor population in the rat central and peripheral lung was found in competition binding experiments against [3H]quinuclidinyl benzilate ([3H]QNB) using the selective antagonists pirenzepine, AF-DX 116 and hexahydrosiladifenidol (HHSiD). Pirenzepine displaced [3H]QNB with low affinity from preparations of central airways indicating the absence of M1receptors in the trachea and bronchi. Muscarinic receptors in the central airways are comprised of both M2and M3receptors since AF-DX 116, an M2-selective antagonist, bound with high affinity to 70% of the available sites while HHSiD, an M3-selective antagonist bound with high affinity to the remaining binding sites. In the peripheral lung, pirenzepine bound with high affinity to 14% of the receptor population, AF-DX 116 bound with high affinity to 79% of the binding sites while HHSiD bound with high affinity to 18% of the binding sites. The presence of M1receptors in the peripheral airways but not in the central airways was confirmed using [3H]telenzepine, an M1receptor ligand. [3H]Telenzepine showed specific saturable binding to 8% of [3H]QNB labeled binding sites in homogenates of rat peripheral lung, while there was no detectable specific binding in homogenates of rat trachea or heart. The results presented here demonnstrate that there are three muscarinic receptor subtypes in rat lungs, and that the distribution of the different subtypes varies within the lungs. Throughout the airways, the dominant muscarinic receptor subtype is M2. In the trachea and bronchi the remaining receptors are M3, while in the peripheral lungs, the remaining receptors are both M1and M3.