Prostaglandin DP receptors positively coupled to adenylyl cyclase in embryonic bovine tracheal (EBTr) cells: pharmacological characterization using agonists and antagonists

1 Various prostaglandin agonists representing various classes of receptor s ubtypes were evaluated for their ability to stimulate adenylyl cyclase via the endogenous DP receptor in embryonic bovine tracheal (EBTr) cells. Two a ntagonists were used to block the agonist-induced cyclic AMP production. 2 ZK118182 (EC50 = 16 +/- 4 nM), RS-93520 (EC50 = 23 +/- 4 nM), SQ27986 (EC 50 = 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 ago nists. Whilst most compounds were full agonists (Emax = 100% relative to PG D(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. c loprostenol; fluprostenol; PHXA85), IP (iloprost; PGI(2)) and TP (U46619) p rostanoid receptor classes were weak agonists or inactive in the EBTr cell assay system. 4 The DP-receptor antagonist, BWA868C, showed a competitive antagonist prof ile 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, respectivel y (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 antago nist prostaglandins. These data support the utility of the EBTr cell line a s a useful tool for the evaluation of DP receptor agonists and antagonists and for profiling other classes of prostaglandins.