Jazayeri A, Meyer W J
University of Texas Medical Branch, Department of Human Biological Chemistry & Genetics, Galveston 77550.
J Steroid Biochem. 1989 Nov;33(5):987-91. doi: 10.1016/0022-4731(89)90250-1.
We have investigated the effect of mineralocorticoids on beta-adrenergic receptors in cultured arterial smooth muscle cells. Mineralocorticoid (aldosterone) treatment resulted in a significant increase in beta-adrenergic receptors measured by [3H]dihydroalprenolol (DHA) binding. This effect required at least 20 hours of incubation with aldosterone and was completely blocked by cycloheximide (10 micrograms/ml), indicating protein synthesis was required for this response. Aldosterone at the concentration range of 10(-8)-10(-6) M increased [3H]DHA binding, but was ineffective at 10(-9) M. Scatchard analysis of [3H]DHA binding revealed that the observed significant increase in binding was due to an increased number of binding sites (P less than 0.05), and that the affinity was unchanged. The aldosterone (1 x 10(-8) M) effect was completely blocked by the combination of RU 38486 (10(-6) M) and spironolactone (10(-7) M), but not by the glucocorticoid antagonist RU 38486 alone. While basal c-AMP levels were not changed by aldosterone (10(-6) M) treatment, the isoproterenol (10(-6) M) stimulated level of c-AMP was significantly higher in cells treated with aldosterone (P less than 0.05). We conclude that aldosterone, acting through the mineralocorticoid receptor, has a direct effect on arterial smooth muscle cells mediated through modulation of beta-adrenergic receptors of these cells.
我们研究了盐皮质激素对培养的动脉平滑肌细胞中β-肾上腺素能受体的影响。用盐皮质激素（醛固酮）处理后，通过[³H]二氢阿普洛尔（DHA）结合法测得的β-肾上腺素能受体显著增加。这种效应至少需要与醛固酮孵育20小时，并且完全被环己酰亚胺（10微克/毫升）阻断，表明该反应需要蛋白质合成。浓度范围在10⁻⁸ - 10⁻⁶ M的醛固酮可增加[³H]DHA结合，但在10⁻⁹ M时无效。对[³H]DHA结合的Scatchard分析表明，观察到的结合显著增加是由于结合位点数量增加（P < 0.05），而亲和力未改变。醛固酮（1×10⁻⁸ M）的效应被RU 38486（10⁻⁶ M）和螺内酯（10⁻⁷ M）的组合完全阻断，但单独使用糖皮质激素拮抗剂RU 38486则不能阻断。虽然醛固酮（10⁻⁶ M）处理未改变基础c-AMP水平，但在用醛固酮处理的细胞中，异丙肾上腺素（10⁻⁶ M）刺激的c-AMP水平显著更高（P < 0.05）。我们得出结论，醛固酮通过盐皮质激素受体起作用，对动脉平滑肌细胞有直接影响，这种影响是通过调节这些细胞的β-肾上腺素能受体介导的。
