PROSTAGLANDIN-STIMULATED ADENYLYL-CYCLASE ACTIVITY VIA A PHARMACOLOGICALLY DEFINED EP2 RECEPTOR IN HUMAN NONPIGMENTED CILIARY EPITHELIAL-CELLS

The goal of these studies was to compare the effects of several prosta glandin (PG) receptor agonists on adenylyl cyclase activity in transfo rmed human nonpigmented ciliary epithelial (NPE) cells. In order to de fine the pharmacology of the PG receptors present on these cells, cycl ic AMP production was measured by both manual and robotic radioimmunoa ssay (RIA) techniques. In NPE cells, the rank order of potency for the PGs tested in the current study (n = up to 46) was PGE(2) (EC50 = 67 nM) > 13,14-dihydro-PGE(1) (EC50 = 231 nM)> 11-deoxy-PGE(1) (EC50 = 50 0 nM) = 16,16-dimethyl-PGE(2) (EC50 = 872 nM) = 11-deoxy-16,16-dimethy l-PGE(2) (EC50 = 1135 nM) >> PGF(2 alpha) (EC50 > 10,000 nM)= PGD(2) ( EC50 > 10,000 nM) = PGI(2) (EC50 > 10,000 nM). The EP2-receptor select ive PG, butaprost, exhibited a potency of 212 nM (E-max = 55%). The re sponse to 1 mu M PGE(2) was antagonized by AH6809 (IC50 = similar to 5 0 mu M, K-b = 4 mu M). The relative potencies of the EP agonists menti oned above were significantly weaker in EbTr and NCB-20 cells expressi ng DP and IP receptors, respectively (1). These data provide a detaile d pharmacological identification and characterization of EP2 receptors on NPE cells.