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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Crider, J. Y. Griffin, B. W. Sharif, N. A. |
| Description | Author Affiliation: Crider JY ( Molecular Pharmacology Unit, Alcon Laboratories, Inc., Fort Worth, Texas 76134-2099, USA.) |
| Abstract | 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. 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 PGD2 (EC50=101+/-10 nM) (n = 4-70) were the most potent agonists. Whilst most compounds were full agonists (Emax = 100% relative to PGD2), BW245C was significantly more efficacious than PGD2 (Emax = 121+/-3%; P<0.001) and RS-93520 appeared to be a partial agonist (Emax = 64+/-9%; P<0.001). Agonists from the EP (e.g. enprostil; misoprostol; butaprost), FP (e.g. cloprostenol; fluprostenol; PHXA85), IP (iloprost; PGI2) and TP (U46619) prostanoid receptor classes were weak agonists or inactive in the EBTr cell assay system. The DP-receptor antagonist, BWA868C, showed a competitive antagonist profile with pA2 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 purported DP-receptor antagonist, weakly inhibited PGD2- and ZK 18182-induced cyclic AMP production (K(i)s = 808+/-193 nM and 782+/-178 nM, respectively). 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. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 127 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-05-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adenylate Cyclase Metabolism Prostaglandin Antagonists Pharmacology Prostaglandin D2 Receptors, Immunologic Receptors, Prostaglandin Trachea Xanthones Adenosine Monophosphate Biosynthesis Adenylyl Cyclase Inhibitors Animals Cells, Cultured Cyclic AMP Embryo, Mammalian Enzyme Inhibitors Hydantoins Agonists Antagonists & Inhibitors Stimulation, Chemical Cytology Drug Effects Enzymology Xanthenes |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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