Barlage, Stefan and Wimmer, Antonia and Pfeiffer, Alexandra and Rothe, Gregor and Schmitz, Gerd (2002) MK-383 (Tirofiban) induces a GPIIb/IIIa receptor conformation which differs from the resting and activated receptor. PLATELETS, 13 (3). pp. 133-140. ISSN 0953-7104
Full text not available from this repository. (Request a copy)Abstract
The platelet integrin alpha(IIb)beta(3) (GPIIb/IIIa) acts as a receptor for fibrinogen, playing a critical role in platelet aggregation. GPIIb/IIIa antagonists, which block the receptor-ligand interaction, have been accused of causing occasional thrombocytopenia, probably via drug-induced platelet activation or immunogenic neoepitopes. We, therefore, analyzed the effects of the GPIIb/IIIa antagonist MK-383 (tirofiban) on platelet activation and GpIIb/IIIa conformation. At a concentration of 10(-7) mol/l, MK-383 completely inhibited fibrinogen binding to in vitro stimulated platelets. Simultaneously, the GPIIb/IIIa expression density increased, similar to that on activated platelets, but no effect on P-selectin expression or the formation of platelet-leukocyte aggregates could be observed, indicating that MK-383 binding did not induce general platelet activation. The GPIIb/IIIa receptor conformation was further analyzed by fluorescence resonance energy transfer analysis between fluorochrome-labeled antibodies against different GpIIb/IIIa epitopes. As a result, MK-383 induced a receptor conformation that differed from the resting as well as the activated receptor as induced by ADP or TRAP-6. This conformational modulation of GPIIb/IIIa presents an interesting mechanism which may be linked to receptor recruitment without inducing general platelet activation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLYCOPROTEIN-IIB-IIIA; PLATELET INTEGRIN ALPHA(IIB)BETA(3); RESONANCE ENERGY-TRANSFER; PROTEIN-TYROSINE KINASE; CORONARY-ARTERY DISEASE; FIBRINOGEN RECEPTOR; IIB/IIIA INHIBITORS; BINDING; AGGREGATION; ANTAGONISTS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Oct 2021 15:10 |
| Last Modified: | 27 Oct 2021 15:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40363 |
Actions (login required)
 |
View Item |
