Roy C, Hall D, Karish M, Ausiello D A
J Biol Chem. 1981 Apr 10;256(7):3423-7.
In intact LLC-PK1 cells, occupancy of vasopressin receptors (Roy, C., and Ausiello, D. A. (1981) J. Biol. Chem. 256, 3415-3522) correlated with cell cAMP production. This relationship was observed as a function of hormone dose, incubation time, and changes in receptor affinity. However, the rate of cAMP production diminished with time in intact cells exposed to high hormone concentrations, even in the presence of a phosphodiesterase inhibitor. A rapid desensitization of adenylate cyclase activity was observed in minutes upon treatment of intact cells with high hormonal concentrations. Desensitization was dose- and time-dependent. Hypertonic sodium chloride, which increased hormonal binding and cell cAMP production, prevented desensitization. The acute decrease in hormone-stimulated adenylate cyclase activity correlated with increased occupancy of low affinity binding sites. EDTA-suspended cells, which have a homogeneous population of binding sites, did not demonstrate desensitization. A proposal is made as to the consequences of this phenomenon at physiological concentrations of vasopressin.
在完整的LLC-PK1细胞中，血管加压素受体的占有率（Roy, C., and Ausiello, D. A. (1981) J. Biol. Chem. 256, 3415 - 3522）与细胞中环磷酸腺苷（cAMP）的产生相关。这种关系可通过激素剂量、孵育时间以及受体亲和力的变化来观察。然而，即使存在磷酸二酯酶抑制剂，暴露于高浓度激素的完整细胞中cAMP的产生速率也会随时间降低。在用高浓度激素处理完整细胞后几分钟内，就观察到腺苷酸环化酶活性迅速脱敏。脱敏呈剂量和时间依赖性。高渗氯化钠可增加激素结合和细胞cAMP的产生，并可防止脱敏。激素刺激的腺苷酸环化酶活性的急性降低与低亲和力结合位点占有率的增加相关。具有均匀结合位点群体的乙二胺四乙酸（EDTA）悬浮细胞未表现出脱敏现象。针对血管加压素生理浓度下这种现象的后果提出了一项建议。
