Prostaglandin D2 interacts at thromboxane receptor-sites on guinea-pig platelets.
The anti-aggregatory prostanoid, prostaglandin D2 (PGD2) does not completely inhibit ADP-induced aggregation of guinea-pig platelets and thus produces a bell-shaped dose-inhibition curve. The nature of this bell-shaped curve has now been investigated in guinea-pig platelet-rich plasma. Two selective thromboxane receptor antagonists, 13-aza-prostanoic acid (13-AZA; 16-64.4 microM) and BM 13.177 (5.9-29.8 microM), converted PGD2 to a full inhibitor of aggregation in a dose-related manner. The putative platelet PGD2 receptor antagonist, N-0164 (75 microM) also converted PGD2 to a full inhibitor of platelet aggregation. In contrast to 13-AZA and BM 13.177, higher concentrations of N-0164 (380 and 760 microM) caused a dose-related rightward shift of the PGD2 dose-inhibition curve. The thromboxane receptor antagonism of N-0164 was confirmed in studies in which the dose-aggregation curve to U-46619, a thromboxane mimetic, was competitively antagonized with a pA2 value of 4.67 and a slope of 1.13, comparable to that of 13-AZA. The results show that N-0164 acts as both a platelet PGD2 and thromboxane-receptor antagonist in both human and guinea-pig platelet-rich plasma. The results further indicate that PGD2 can interact at thromboxane receptors in guinea-pig platelets.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D015230:Prostaglandin D2; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011457:Prostaglandins D / Q000097:blood*; D011466:Prostanoic Acids / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000494:pharmacology
D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D011457:Prostaglandins D; D011466:Prostanoic Acids; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; C012641:N 0164; D000244:Adenosine Diphosphate; C022574:13-azaprostanoic acid; C040624:sulotroban; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015230:Prostaglandin D2