Characterization of muscarinic agonists in recombinant cell lines.
Characterization of muscarinic agonists in recombinant cell lines.
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重组细胞系中毒蕈碱激动剂的表征。
DOI：
10.1016/0024-3205(93)90303-k
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发表时间：
1993
期刊：
影响因子：
6.1
通讯作者：
A. Thomas
中科院分区：
文献类型：
--
作者：
R. Schwarz;R. Davis;J. Jaén;C. Spencer;H. Tecle;A. Thomas
使用表达Hm 1-Hm 5受体的重组CHO细胞，在受体结合和第二信使试验中对参比毒蕈碱激动剂的活性进行了表征。在全细胞[3 H]-N-甲基东莨菪碱结合中，未发现激动剂具有真正的亚型选择性，尽管一些激动剂在几种亚型之间显示出显著差异（例如，m1与m2）。作为受体激活的功能指标，测量了m1、m3和m5受体的磷脂酰肌醇（PI）转换率，同时测量了m2和m4受体对毛喉素刺激的cAMP积累的抑制作用。完全和部分激动剂都描绘了PI营业额，但所有激动剂对cAMP的反应相似。用丙基苄基胆碱芥子气的烷基化研究表明，在功能测定中，游离受体的数量显著影响功效和效力。因此，受体储备似乎在使用功能措施确定激动剂的亚型选择性中发挥重要作用。然而，即使有这些限制，使用转化的细胞系在发现选择性激动剂中发挥着关键作用。
Using recombinant CHO cells that express Hm1 – Hm5 receptors, reference muscarinic agonists have been characterized with respect to their activity in receptor binding and second messenger assays. In whole cell [3H]-N-methyl scopolamine binding, no agonist was found to be truly subtype selective, although some showed marked differences between several of the subtypes (e.g. m1 vs. m2). As a functional index of receptor activation, phosphatidylinositol (PI) turnover was measured for m1, m3, and m5 receptors while inhibition of forskolin-stimulated cAMP accumulation was measured for m2 and m4 receptors. Both full and partial agonists were delineated in PI turnover, but all agonists showed similar responses on cAMP. Alkylation studies with propylbenzylcholine mustard showed that both efficacy and potency were markedly affected in the functional assays by the number of free receptors. Thus, receptor reserve appears to play a major role in the determination of subtype selectivity for agonists using functional measures. Even with these limitations, however, the use of transformed cell lines is playing a pivotal role in the discovery of selective agonists.
体内氧化震颤素类似物受体储备的区域差异：对选择性毒蕈碱激动剂开发的影响。
DOI：
--
发表时间：
1987
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Ringdahl,B;Roch,M;Jenden,DJ
通讯作者：
Jenden,DJ