BW A868C对前列腺素D2的拮抗作用以及BW245C对人血小板腺苷酸环化酶的激活作用。
The antagonism by BW A868C of PGD2 and BW245C activation of human platelet adenylate cyclase.
作者信息
Trist D G, Collins B A, Wood J, Kelly M G, Robertson A D
机构信息
Department of Biochemistry, Wellcome Research Laboratories, Beckenham, Kent.
出版信息
Br J Pharmacol. 1989 Feb;96(2):301-6. doi: 10.1111/j.1476-5381.1989.tb11817.x.
Abstract
- In glycerol-lysed human platelets, prostaglandin D2 (PGD2) and the hydantoin BW245C both activate adenylate cyclase in a biphasic manner. These activations are qualitatively different from those of carbacyclin, iloprost and prostaglandin E2 (PGE2) whose E/[A] curves can be adequately described by rectangular hyperbolae. 2. Prostaglandin E1 (PGE1) had E/[A] curves of slope significantly lower than that expected for a rectangular hyperbolae. 2. Prostaglandin E1 (PGE1) had E/[A] curves of slope significantly lower than that expected for a rectangular hyperbola. 3. The selective PGD2 antagonist BW A868C shifts the first phase of the PGD2 and BW245C E/[A] curves but has no effect on the second phase. 4. Applying a two-receptor model enables a pKB to be derived for BW A868C of 9.11. 5. BW A868C has no effect on carbacyclin, iloprost, prostacyclin, PGE1 and PGE2 at a concentration 1,000 fold that of its KB against PGD2 and BW245C. 6. These results indicate that PGD2 and BW245C are capable of activating adenylate cyclase in human platelets through the DP-receptor and by another mechanism as yet uncharacterized.
摘要
- 在甘油溶解的人血小板中，前列腺素D2（PGD2）和乙内酰脲BW245C均以双相方式激活腺苷酸环化酶。这些激活在性质上不同于卡前列环素、伊洛前列素和前列腺素E2（PGE2），它们的E/[A]曲线可用矩形双曲线充分描述。2. 前列腺素E1（PGE1）的E/[A]曲线斜率明显低于矩形双曲线预期值。2. 前列腺素E1（PGE1）的E/[A]曲线斜率明显低于矩形双曲线预期值。3. 选择性PGD2拮抗剂BW A868C使PGD2和BW245C的E/[A]曲线的第一相发生位移，但对第二相无影响。4. 应用双受体模型可得出BW A868C的pKB为9.11。5. BW A868C在其针对PGD2和BW245C的KB浓度的1000倍浓度下，对卡前列环素、伊洛前列素、前列环素、PGE1和PGE2无影响。6. 这些结果表明，PGD2和BW245C能够通过DP受体并通过另一种尚未明确的机制激活人血小板中的腺苷酸环化酶。
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