Crider J Y, Griffin B W, Sharif N A
Molecular Pharmacology Unit, Alcon Laboratories, Inc., Fort Worth, Texas, USA.
J Ocul Pharmacol Ther. 1998 Aug;14(4):293-304. doi: 10.1089/jop.1998.14.293.
The goal of these studies was to compare the effects of several prostaglandin (PG) receptor agonists on adenylyl cyclase activity in transformed human nonpigmented ciliary epithelial (NPE) cells. In order to define the pharmacology of the PG receptors present on these cells, cyclic AMP production was measured by both manual and robotic radioimmunoassay (RIA) techniques. In NPE cells, the rank order of potency for the PGs tested in the current study (n = up to 46) was PGE2 (EC50 = 67 nM) > 13,14-dihydro-PGE1 (EC50 = 231 nM) > 11-deoxy-PGE1 (EC50 = 500 nM) = 16,16-dimethyl-PGE2 (EC50 = 872 nM) = 11-deoxy-16,16-dimethyl-PGE2 (EC50 = 1135 nM) >> PGF2 alpha (EC50 > 10,000 nM) = PGD2 (EC50 > 10,000 nM) = PGI2 (EC50 > 10,000 nM). The EP2-receptor selective PG, butaprost, exhibited a potency of 212 nM (Emax = 55%). The response to 1 microM PGE2 was antagonized by AH6809 (IC50 = approximately 50 microM, Kb = 4 microM). The relative potencies of the EP agonists mentioned above were significantly weaker in EbTr and NCB-20 cells expressing DP and IP receptors, respectively (1). These data provide a detailed pharmacological identification and characterization of EP2 receptors on NPE cells.
这些研究的目的是比较几种前列腺素（PG）受体激动剂对转化的人非色素睫状上皮（NPE）细胞中腺苷酸环化酶活性的影响。为了确定这些细胞上存在的PG受体的药理学特性，通过手动和机器人放射免疫测定（RIA）技术测量了环磷酸腺苷（cAMP）的产生。在NPE细胞中，本研究中测试的PGs（n = 最多46）的效价顺序为：前列腺素E2（PGE2，半数有效浓度[EC50]=67 nM）＞13,14-二氢前列腺素E1（13,14-dihydro-PGE1，EC50 = 231 nM）＞11-脱氧前列腺素E1（11-deoxy-PGE1，EC50 = 500 nM）= 16,16-二甲基前列腺素E2（16,16-dimethyl-PGE2，EC50 = 872 nM）= 11-脱氧-16,16-二甲基前列腺素E2（11-deoxy-16,16-dimethyl-PGE2，EC50 = 1135 nM）＞＞前列腺素F2α（PGF2 alpha，EC50＞10,000 nM）= 前列腺素D2（PGD2，EC50＞10,000 nM）= 前列环素（PGI2，EC50＞10,000 nM）。EP2受体选择性PG布他前列素的效价为212 nM（最大效应[Emax]=55%）。AH6809拮抗了对1 μM PGE2的反应（IC50 = 约50 μM，平衡解离常数[Kb]=4 μM）。上述EP激动剂的相对效价在分别表达DP和IP受体的EbTr细胞和NCB-20细胞中显著较弱（1）。这些数据提供了NPE细胞上EP2受体详细的药理学鉴定和特征描述。
