pH-dependent binding of the TXA2/PGH2-receptor of human platelet membranes to various ligands.
[3H]-BAY U 3405 was used to characterize the pH-dependency of the binding of various ligands to the TXA2/PGH2-receptor of human platelet membranes. Maximum binding of [3H]-BAY U 3405 is achieved at pH 5.8. In inhibition studies the ligands Daltroban, CTA2, and U 46619 also show a higher affinity at pH 5.8 compared to pH 7.4. In contrast, the ligands I-PTA-OH and GR 32191 have a higher affinity at pH 7.4. No difference is seen with SQ 29548. The ligands I-PTA-OH, GR 32191, and SQ 29548 have a second protonable group in common, which is thought to be the reason for the different pH-dependent binding.
Theis
J G
JG
Institut für Herz/Kreislauf- und Artheroskleroseforschung, Bayer AG, Wuppertal, Germany.
Dellweg
H
H
Perzborn
E
E
Gross
R
R
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001792:Blood Platelets / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D010648:Phenylacetates / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism* / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002227:Carbazoles; D008024:Ligands; D010648:Phenylacetates; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D044262:Prostaglandin H2; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C063119:ramatroban; C051762:daltroban