Nerme V, Abrahamsson T, Vauquelin G
Department of Cardiovascular Pharmacology, Hässle Research Laboratories, Möindal, Sweden.
Arch Int Pharmacodyn Ther. 1989 Sep-Oct;301:51-65.
Preincubation of guinea-pig lung membranes with the beta-agonist isoprenaline or with the partial beta-agonist terbutaline, followed by repeated washing, causes a 35% decrease in the number of beta-adrenoceptors (R). This decrease corresponds to the tight binding of the agonist (H) to R as a result of the formation of a complex between H.R. and the stimulatory guanine nucleotide regulatory component (Ns). Tight binding of the agonist is dependent on the presence of magnesium ions and is reversed by GTP. However, the stability of the H.R.Ns-complex is limited even in the absence of GTP. Under these conditions, the complex is more stable when induced by isoprenaline than by terbutaline. When the alkylating reagent N-ethylmaleimide is included in the agonist preincubation step, tight binding of isoprenaline and terbutaline is increased to about 55% of the receptor population and is no longer dependent on the presence of magnesium ions. This value is in good agreement with the percentage of agonist high affinity sites, determined by isoprenaline/[3H]-dihydroalprenolol competition binding studies.
用β-激动剂异丙肾上腺素或部分β-激动剂特布他林对豚鼠肺膜进行预孵育，随后反复洗涤，会导致β-肾上腺素能受体（R）数量减少35%。这种减少对应于激动剂（H）与R的紧密结合，这是由于H.R.与刺激性鸟嘌呤核苷酸调节成分（Ns）形成复合物的结果。激动剂的紧密结合依赖于镁离子的存在，并可被GTP逆转。然而，即使在没有GTP的情况下，H.R.Ns复合物的稳定性也是有限的。在这些条件下，由异丙肾上腺素诱导形成的复合物比由特布他林诱导形成的复合物更稳定。当在激动剂预孵育步骤中加入烷基化试剂N-乙基马来酰亚胺时，异丙肾上腺素和特布他林的紧密结合增加到受体总数的约55%，并且不再依赖于镁离子的存在。该值与通过异丙肾上腺素/[3H]-二氢阿普洛尔竞争结合研究确定的激动剂高亲和力位点的百分比非常一致。
