Van Haastert P J
J Biol Chem. 1987 Jun 5;262(16):7705-10.
cAMP induces the activation and subsequent desensitization of adenylate cyclase in Dictyostelium discoideum. cAMP also induces down-regulation of surface cAMP receptors. Desensitization of adenylate cyclase is composed of a rapidly reversible component (adaptation) and a slowly reversible component related to down-regulation of surface cAMP receptors (Van Haastert, P.J.M. (1987) J. Biol. Chem. 262, 7700-7704). The agonistic and antagonistic activities of the cAMP derivative adenosine 3',5'-monophosphorothioate ((Rp)-cAMPS) for these responses were investigated. (Rp)-cAMPS competes with cAMP for binding to different receptor forms with an apparent Ki = 5 microM. (Rp)-cAMPS does not activate adenylate cyclase and antagonizes the cAMP-induced activation with an apparent Ki = 5 microM. (Rp)-cAMPS induces down-regulation of surface cAMP receptors with EC50 = 5 microM. (Rp)-cAMPS induces desensitization of adenylate cyclase, which is not rapidly reversible. These results indicate that desensitization of adenylate cyclase by (Rp)-cAMPS is due to down-regulation of surface cAMP receptors and not to adaptation. We conclude that down-regulation of surface cAMP receptors does not require their activation or modification involved in adaptation.
环磷酸腺苷（cAMP）可诱导盘基网柄菌中腺苷酸环化酶的激活及随后的脱敏作用。cAMP还可诱导表面cAMP受体的下调。腺苷酸环化酶的脱敏作用由一个快速可逆成分（适应性）和一个与表面cAMP受体下调相关的缓慢可逆成分组成（范·哈斯特，P.J.M.（1987年）《生物化学杂志》262卷，7700 - 7704页）。研究了cAMP衍生物3',5'-单磷酸硫代腺苷（（Rp）-cAMPS）对这些反应的激动和拮抗活性。（Rp）-cAMPS与cAMP竞争结合不同的受体形式，其表观解离常数Ki = 5微摩尔。（Rp）-cAMPS不激活腺苷酸环化酶，并以表观解离常数Ki = 5微摩尔拮抗cAMP诱导的激活作用。（Rp）-cAMPS以半数有效浓度EC50 = 5微摩尔诱导表面cAMP受体的下调。（Rp）-cAMPS诱导腺苷酸环化酶的脱敏作用，这不是快速可逆的。这些结果表明，（Rp）-cAMPS对腺苷酸环化酶的脱敏作用是由于表面cAMP受体的下调，而不是适应性。我们得出结论，表面cAMP受体的下调不需要其参与适应性的激活或修饰。
