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.