ADP-, PAF- and adrenaline-induced platelet aggregation and thromboxane formation are not affected by a thromboxane receptor antagonist at physiological external Ca++ concentrations.
Thromboxane (TX) receptor antagonists are of considerable clinical interest in prevention of acute thrombembolic vessel occlusion. This study demonstrates that the selective TX receptor antagonist, daltroban, at a concentration (10 microM) that does not inhibit TX synthesis, markedly inhibits ADP-, PAF- and adrenaline-induced platelet secretion and TX formation. With the exception of ADP-induced platelet secretion, these actions are only detectable in citrated platelet-rich plasma but not in plasma anticoagulated by hirudin. Since TX antagonists are supposed to act at physiological external Ca++ concentrations in the clinics, it is questionable whether in vitro studies in Ca(++)-deprived media are the optimum model to evaluate the clinical potential of these compounds.
Bretschneider
E
E
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Glusa
E
E
Schrör
K
K
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D019343:Citric Acid; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D005947:Glucose / Q000031:analogs & derivatives / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D013931:Thromboxanes / Q000096:biosynthesis*
D006629:Hirudins; D010648:Phenylacetates; D010972:Platelet Activating Factor; D017482:Receptors, Thromboxane; D011994:Recombinant Proteins; D013449:Sulfonamides; D013931:Thromboxanes; C002113:acid citrate dextrose; D019343:Citric Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003094:Collagen; D005947:Glucose; C051762:daltroban; D002118:Calcium; D007213:Indomethacin; D004837:Epinephrine