表征的重组人类前列腺素类l - 644698 DP受体和识别,小说选择性DP受体激动剂。
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赖特DH, Metters公里,Abramovitz M, Ford-Hutchinson哦
表征的重组人类前列腺素类l - 644698 DP受体和识别,小说选择性DP受体激动剂。
Br J杂志。1998年4月,123 (7):1317 - 24。
- PubMed ID
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9579725 (在PubMed]
- 文摘
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1。人类胚胎肾细胞系[HEK 293 (EBNA)]稳定表达人类重组前列腺素D2 (PGD2)受体(黄芪丹参滴丸)对放射性配体结合特征和信号转导属性使用前列腺素类和前列腺素类的类似物。放射性配体结合的研究包括饱和度分析核苷酸类似物的影响,初始速率中的协会和均衡的竞争分析。此外,3”:5 '环一磷酸腺苷(环腺苷酸)生成配位反应的挑战也测量,因为这是主要的黄芪丹参滴丸信号通路。2。l - 644698 ((4 - (3 - (3 - (3-hydroxyoctyl) 4-oxo-2-thiazolidinyl)丙基)苯甲酸)(外消旋体))被确认为一种新型配体有较高的亲和力与抑制剂黄芪丹参滴丸常数(Ki) 0.9海里。这个吻值是与配体的Ki价值观这一研究获得的DP:以前显示高度的亲和力PGD2(0.6海里),ZK 110841 (0.3 nM), BW245C(0.4海里),和BW A868C(2.3海里)。3所示。l - 644698被发现一个完整的受体激动剂0.5 nM的EC50值生成环腺苷酸活化后黄芪丹参滴丸。因此,l - 644698与那些与已知的功效在DP受体受体激动剂(EC50): PGD2(0.5海里),ZK 110841 (0.2 nM)和BW245C(0.3海里)。 4. L-644,698 displayed a high degree of selectivity for hDP when compared to the family of cloned human prostanoid receptors: EP1 (> 25,400 fold), EP2 (approximately 300 fold), EP3-III (approximately 4100 fold), EP4 (approximately 10000 fold), FP (> 25,400 fold), IP (> 25,400 fold) and TP (> 25,400 fold). L-644,698 is, therefore, one of the most selective DP agonists as yet described. 5. PGJ2 and delta12-PGJ2, two endogenous metabolites of PGD2, were also tested in this system and shown to be effective agonists with Ki and EC50 values in the nanomolar range for both compounds. In particular, PGJ2 was equipotent to known DP specific agonists with a Ki value of 0.9 nM and an EC50 value of 1.2 nM.