Prostaglandin DP receptors positively coupled to adenylyl cyclase in embryonic bovine tracheal (EBTr) cells: pharmacological characterization using agonists and antagonists
Prostaglandin DP receptors positively coupled to adenylyl cyclase in embryonic bovine tracheal (EBTr) cells: pharmacological characterization using agonists and antagonists
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DOI：
10.1038/sj.bjp.0702490
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发表时间：
1999-05-01
影响因子：
7.3
通讯作者：
Sharif, NA
中科院分区：
文献类型：
--
作者：
Crider, JY;Griffin, BW;Sharif, NA
1评价了代表各种受体亚型的各种前列腺素激动剂通过胚胎牛气管（EBTr）细胞中的内源性DP受体刺激腺苷酸环化酶的能力。两种拮抗剂用于阻断激动剂诱导的环AMP产生。2 ZK 118182（EC50 = 16 +/- 4 nM），RS-93520（EC50 = 23 +/- 4 nM），SQ27986（EC 50 = 33 +/- 9 nM）、ZK 110841（EC 50 = 33 +/- 5 nM）、BW 245 C（EC 50 = 59 +/- 19 nM）和PGD（2）（EC 50 = 101 +/- 10 nM）（n = 4 - 70）是最有效的激动剂。虽然大多数化合物是完全激动剂，（相对于PGD（2），Emax = 100%），BW 245 C比PGD（2）显著更有效（E-max = 121 +/- 3%; P < 0.001），RS-93520似乎是部分激动剂（E-max = 64 +/- 9%; P < 0.001）。3来自EP的激动剂（例如，恩前列素;米索前列醇;布他前列素），FP（例如氯前列醇;氟前列醇; PHXA 85），IP（伊洛前列素; PGI（2））和TP（U46619）前列腺素类受体在EBTr细胞测定系统中是弱激动剂或无活性的。在使用两种结构不同的激动剂BW 245 C和ZK 118182的Schild分析中，显示出竞争性拮抗剂特征，pA（2）值分别为8.00 +/- 0.02和8.14 +/- 0.13（n = 3）。AH 6809是另一种预期的DP受体拮抗剂，可微弱抑制PGD（2-）和ZK 118182诱导的环AMP产生（K（i）s分别为808 +/- 193 nM和782 +/- 178 nM）。5目前的研究已使用广泛的激动剂和拮抗剂野牡丹素对EBTr细胞中与腺苷酸环化酶正偶联的DP受体进行了表征。这些数据支持EBTr细胞系作为评价DP受体激动剂和拮抗剂以及分析其他类别的野牡丹素的有用工具的效用。
1 Various prostaglandin agonists representing various classes of receptor subtypes were evaluated for their ability to stimulate adenylyl cyclase via the endogenous DP receptor in embryonic bovine tracheal (EBTr) cells. Two antagonists were used to block the agonist-induced cyclic AMP production.2 ZK118182 (EC50 = 16 +/- 4 nM), RS-93520 (EC50 = 23 +/- 4 nM), SQ27986 (EC50 = 33 +/- 9 nM), ZK110841 (EC50 = 33 +/- 5 nM), BW245C (EC50 = 59 +/- 19 nM) and PGD(2) (EC50 = 101 +/- 10 nM) (n = 4 - 70) were the most potent agonists. Whilst most compounds were full agonists (Emax = 100% relative to PGD(2)), BW245C was significantly more efficacious than PGD(2) (E-max = 121 +/- 3%; P < 0.001) and RS-93520 appeared to be partial agonist (E-max = 64 +/- 9%; P < 0.001).3 Agonists from the EP (e.g. enprostil; misoprostol; butaprost), FP (e.g. cloprostenol; fluprostenol; PHXA85), IP (iloprost; PGI(2)) and TP (U46619) prostanoid receptor classes were weak agonists or inactive in the EBTr cell assay system.4 The DP-receptor antagonist, BWA868C, showed a competitive antagonist profile with pA(2) values of 8.00 +/- 0.02 and 8.14 +/- 0.13 in Schild analyses with two structurally different agonists, BW245C and ZK118182, respectively (n = 3). AH6809, another purpoted DP-receptor antagonist weakly inhibited PGD(2-) and ZK118182-induced cyclic AMP production (K(i)s = 808 +/- 193 nM and 782 +/- 178 nM, respectively).5 The current studies have characterized the DP receptor positively coupled to adenylyl cyclase in EBTr cells using a wide range of agonist and antagonist prostaglandins. These data support the utility of the EBTr cell line as a useful tool for the evaluation of DP receptor agonists and antagonists and for profiling other classes of prostaglandins.