Abstract 13598: The G-protein BetaGamma Subunits Regulate Platelet Function Academic Article uri icon


  • Platelet activation involves tightly regulated processes to ensure a proper hemostasis response, but when unbalanced, can lead to pathological consequences such as thrombus formation. G-protein coupled receptors (GPCRs) regulate platelet function by interacting with and mediating the response to various physiological agonists. To this end, an essential mediator of GPCR signaling is the G protein G heterotrimers, in which the subunits are central players in downstream signaling pathways. While much is known regarding the role of the G subunit in platelet function, that of the remains poorly understood. Therefore, we investigated the role of G subunits in platelet function using a G (small molecule) inhibitor, namely gallein. We observed that gallein inhibits platelet aggregation and secretion in response to agonist stimulation, in both mouse and human platelets. Furthermore, gallein also exerted inhibitory effects on integrin IIb3 activation and clot retraction. Finally, galleins inhibitory effects manifested in vivo , as documented by its ability to modulate physiological hemostasis and delay thrombus formation. Taken together, our findings demonstrate, for the first time, that G directly regulates GPCR-dependent platelet function, in vitro and in vivo . Moreover, these data highlight G as a novel therapeutic target for managing thrombotic disorders.

published proceedings

  • Circulation

author list (cited authors)

  • Alarabi, A., Karim, Z., Hinojos, V., Lozano, P. A., Hernandez, K., Montes Ramirez, J., Khasawneh, F. T., & Alshbool, F. Z.

citation count

  • 0

complete list of authors

  • Alarabi, Ahmed||Karim, Zubair||Hinojos, Victoria||Lozano, Patricia A||Hernandez, Keziah||Montes Ramirez, Jean||Khasawneh, Fadi T||Alshbool, Fatima Z

publication date

  • January 2020