Evaluation of ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, with a PGD2-responsive cell line from bovine embryonic trachea.
ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, were evaluated with a fibroblastic cell line from bovine embryonic trachea (EBTr) which specifically responds to prostaglandin D2 (PGD2). ZK110841, equipotent to PGD2, elevated the adenosine 3':5'-cyclic monophosphate (cyclic AMP) level in EBTr cells dose-dependently, being more than 100 fold over the basal level at 1 microM. The half-maximally effective concentration of PGD2 or ZK110841 was 10-30 nM. Increasing concentrations (10(-7)-10(-4) M) of AH6809 (which possesses negligible intrinsic agonist activity) produced parallel shifts to the right of dose-response curves to PGD2 and ZK110841. Schild plots of these data were linear (correlation close to unity) and pA2 values against PGD2 and ZK110841 were calculated to be 6.36 and 6.57, respectively, indicating that AH6809 is a simple and competitive antagonist. These results demonstrate that ZK110841, AH6809 and EBTr cells will be useful for characterization of DP-receptors.
Ito
S
S
Department of Cell Biology, Osaka Bioscience Institute, Suita, Japan.
Okuda
E
E
Sugama
K
K
Negishi
M
M
Hayaishi
O
O
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
D011982:Receptors, Prostaglandin; D014966:Xanthenes; D044004:Xanthones; C061300:ZK 110841; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D015237:Dinoprost; D000242:Cyclic AMP; D015230:Prostaglandin D2