Yasunari K, Kohno M, Yokokawa K, Horio T, Kano H, Takeda T
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Hypertens Res. 1995 Jun;18 Suppl 1:S29-33. doi: 10.1291/hypres.18.supplementi_s29.
The modulation of dopamine DA1 receptors of cultured rat renal arterial smooth muscle cells by phorbol ester, glucocorticoid and sodium chloride was studied. The extent of [3H]Sch-23390 binding to phorbol ester-treated cell was increased without any change in the dissociation constant (Kd). At a concentration of 10 nmol/l, the synthetic glucocorticoid dexamethasone increased maximum receptor binding (Bmax) but had no effect on the Kd. 100 mmol/l sodium chloride did not change Bmax, but increased the Kd for DA1 receptor. The production of cAMP in response to DA1 receptor stimulation was enhanced without any change of the adenylate cyclase activity. The glucocorticoid effect on DA1 of arterial smooth muscle cells became apparent after hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximide (10 micrograms/ml) and by the glucocorticoid receptor antagonist RU-38486, indicating that the effect required protein synthesis through glucocorticoid receptors. Treatment of cells with 1 mumol/l dexamethasone for 24 h increased basal and DA1-stimulated adenylate cyclase activity. Basal adenylate cyclase was decreased by sodium chloride in a dose-dependent manner. These results suggest differential control of DA1 receptors on vascular smooth muscle cells by protein kinase C, glucocorticoid or sodium chloride.
研究了佛波酯、糖皮质激素和氯化钠对培养的大鼠肾动脉平滑肌细胞多巴胺DA1受体的调节作用。[3H]Sch-23390与佛波酯处理细胞的结合程度增加，而解离常数（Kd）无任何变化。在浓度为10 nmol/l时，合成糖皮质激素地塞米松增加了最大受体结合量（Bmax），但对Kd无影响。100 mmol/l氯化钠未改变Bmax，但增加了DA1受体的Kd。对DA1受体刺激产生的cAMP生成增加，而腺苷酸环化酶活性无任何变化。在存在类固醇的情况下孵育数小时后，糖皮质激素对动脉平滑肌细胞DA1的作用变得明显，并且被环己酰亚胺（10微克/毫升）和糖皮质激素受体拮抗剂RU-38486显著抑制，表明该作用需要通过糖皮质激素受体进行蛋白质合成。用1微摩尔/升地塞米松处理细胞24小时可增加基础和DA1刺激的腺苷酸环化酶活性。基础腺苷酸环化酶被氯化钠以剂量依赖的方式降低。这些结果表明蛋白激酶C、糖皮质激素或氯化钠对血管平滑肌细胞上的DA1受体有不同的调控作用。
