Hanasaki K, Mizuno Y, Ikeda M, Shimonishi M, Yoshimura S, Tomita K, Ichikawa A
Biochim Biophys Acta. 1987 Feb 18;927(2):261-8. doi: 10.1016/0167-4889(87)90143-1.
[3H]Prostaglandin D2 binding to rabbit platelets was increased by about 150% in the presence of beta-adrenoceptor agonist, isoproterenol. The isoproterenol-induced potentiation of the [3H]prostaglandin D2 binding gave a bell-shaped dose-response relationship (maximum response at 3 X 10(-8) M) in a stereospecific manner. Similar and moderate potentiation was obtained with terbutaline. On the other hand, beta-adrenoceptor antagonists such as alprenolol, propranolol and butoxamine (beta 2-specific) had no potentiating effect on [3H]prostaglandin D2 binding; rather, they abolished the isoproterenol-induced increase of [3H]prostaglandin D2 binding. The beta 1-specific antagonist, metoprolol, did not have any effect. Rabbit platelets were found to possess one [3H]prostaglandin D2 binding site (Kd = 6 X 10(-7) M, Bmax = 787 fmol/mg protein). In the presence of isoproterenol at 3 X 10(-8) M, Bmax was increased with unaltering Kd value. Isoproterenol did not increase [3H]prostaglandin E1, [3H]prostaglandin E2 and [3H]prostaglandin F2 alpha bindings to platelets. The potential effect of isoproterenol was mimicked by forskolin, theophylline, dibutyryl cyclic AMP, prostaglandin E1 and prostaglandin I2, but it was abolished by 2', 5'-dideoxyadenosine, an inhibitor of adenylate cyclase, indicating that elevated level of cyclic AMP may be available for the induction of the increase of [3H]prostaglandin D2 binding. Prostaglandin D2-induced cyclic AMP synthesis and antiaggregation activity were also augmented in the presence of isoproterenol. These results suggest a beta 2-adrenoceptor-mediated cyclic AMP-dependent mechanism for the regulation of prostaglandin D2 receptor binding in rabbit platelets.
在β-肾上腺素受体激动剂异丙肾上腺素存在的情况下，[3H]前列腺素D2与兔血小板的结合增加了约150%。异丙肾上腺素诱导的[3H]前列腺素D2结合增强以立体特异性方式呈现钟形剂量-反应关系（在3×10(-8) M时达到最大反应）。特布他林也获得了类似且适度的增强作用。另一方面，β-肾上腺素受体拮抗剂如阿普洛尔、普萘洛尔和丁氧胺（β2特异性）对[3H]前列腺素D2结合没有增强作用；相反，它们消除了异丙肾上腺素诱导的[3H]前列腺素D2结合增加。β1特异性拮抗剂美托洛尔没有任何作用。发现兔血小板具有一个[3H]前列腺素D2结合位点（Kd = 6×10(-7) M，Bmax = 787 fmol/mg蛋白）。在3×10(-8) M的异丙肾上腺素存在下，Bmax增加而Kd值不变。异丙肾上腺素没有增加[3H]前列腺素E1、[3H]前列腺素E2和[3H]前列腺素F2α与血小板的结合。异丙肾上腺素的潜在作用被福斯可林、茶碱、二丁酰环磷腺苷、前列腺素E1和前列腺素I2模拟，但被腺苷酸环化酶抑制剂2', 5'-二脱氧腺苷消除，这表明环磷腺苷水平升高可能参与诱导[3H]前列腺素D2结合增加。在异丙肾上腺素存在下，前列腺素D2诱导的环磷腺苷合成和抗聚集活性也增强。这些结果提示了一种β2-肾上腺素受体介导的环磷腺苷依赖性机制，用于调节兔血小板中前列腺素D2受体的结合。
