沙美特罗和福莫特罗对腺苷酸环化酶的激活作用

Stimulative effects of salmeterol and formoterol on adenylate cyclase1

为研究新长效支气管扩张剂沙美特罗和福莫特罗对腺苷酸环化酶的激活作用，以及福莫特罗的受体选择性，运用双柱离子交换层析法测定福莫特罗和沙美特罗作用于牛支气管平滑肌细胞膜和人肺细胞膜，刺激腺苷酸环化酶生成ｃＡＭＰ的效应．结果表明，福莫特罗激活腺苷酸环化酶的内在活性为高效激动剂异丙肾上腺素的９７．５％，而沙美特罗仅为８１．６％．β２受体拮抗剂ＩＣＩ１１８５５１和沙美特罗均可使福莫特罗生成ｃＡＭＰ的剂量效应曲线向高浓度方向移动，说明福莫特罗为高效激动剂，具有β２受体选择性，而沙美特罗为部分激动剂．

To study the stimulative effects of salmeterol and formoterol on adenylate cyclase and the receptor selectivity of formoterol, the cAMP production of calf tracheal smooth muscle membrane and human lung cell membrane was determined with dual column chromatography. The intrinsic activity of formoterol and salmeterol to induce cAMP was found being 97.5% and 81.6% respectively compared to that (100%) of full agonist isoproterenol. β2Receptor antagonist ICI 118551 and salmeterol shifted the dose response curve of formoterol towards the direction of the high doses. Formoterol showed full agonist characteristics, whereas salmeterol showed partial agonist characteristics. Formoterol was β2selective. Salmeterol inhibited the effect of formoterol competitively.