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目的旨在比较长效支气管扩张剂福莫特罗(FOR)、沙美特罗(SLM)与短效支气管扩张剂芬诺特罗(FEN)、沙丁胺醇(SAL)及异丙肾上腺素(ISO)的内在活性(intrinsic activity,IA),受体亲和力及其在细胞膜的信号放大作用。方法采用酶解法制备牛支气管平滑肌细胞膜,以~(32)P-ATP为底物,测定各激动剂作用于β_2受体,激活腺苷酸环化酶生成cAMP的IA及其生成半数最大量cAMP所需浓度(EC_(50)),并计算出各激动剂的相对效应pEC_(50);以放射性标记配体法测定各激动剂与β_2受体亲和力。结果 ISO、FOR、SLM、FEN和SAL的IA分别为1.00、1.00、0.76、0.81和0.83,上述各激动剂的亲和力分别为6.69、8.02、8.43、5.84和5.84 mol/L,pEC_(50)分别为7.68、9.10、8.70、6.79和6.78 mol/L。结论 FOR与ISO一样,为高效激动剂,其亲和力比ISO高约20倍,其他激动剂为部分激动剂。各激动剂作用于细胞膜均可产生信号放大作用,以FOR为著。FOR的高IA和高亲和力及其在细胞膜的信号放大作用可能是其长效作用的机制之一。
The purpose of this study was to compare the effects of long-acting bronchodilators formoterol (FOR), salmeterol (SLM) and the short-acting bronchodilators fenoterol (FEN), salbutamol (SAL) and isoproterenol Intrinsic activity (IA), receptor affinity and its signal amplification in the cell membrane. Methods The membrane of bovine bronchial smooth muscle cells was prepared by enzymatic hydrolysis. The effect of each agonist on the β_2 receptor was determined by using ~ (32) P-ATP as a substrate. The amount of cAMP produced by adenylyl cyclase and the maximum amount of cAMP (EC 50). The relative effect of each agonist pEC 50 was calculated. The affinity of each agonist to β 2 receptor was determined by radiolabeled ligand method. Results The IA of ISO, FOR, SLM, FEN and SAL were 1.00, 1.00, 0.76, 0.81 and 0.83, respectively. The affinities of the above agonists were 6.69,8.02,8.43,5.84 and 5.84 mol / L, 7.68, 9.10, 8.70, 6.79 and 6.78 mol / L. Conclusion FOR, like ISO, is a high-potency agonist with approximately 20-fold higher affinity than ISO and other agonists as partial agonists. Each agonist acts on the cell membrane can produce signal amplification, with FOR as. The high IA and high affinity of FOR and its signal amplification at the cell membrane may be one of the mechanisms of its long-acting effects.