title: Defective platelet activation in G alpha(q)-deficient mice.
abstract: Platelets are small disc-shaped cell fragments which undergo a rapid transformation when they encounter vascular damage. They become more spherical and extrude pseudopodia, their fibrinogen receptors are activated, causing them to aggregate, they release their granule contents, and eventually form a plug which is responsible for primary haemostasis. Activation of platelets is also implicated in the pathogenesis of unstable angina, myocardial infarction and stroke. Here we show that platelets from mice deficient in the alpha-subunit of the heterotrimeric guanine-nucleotide-binding protein Gq are unresponsive to a variety of physiological platelet activators. As a result, G alpha(q)-deficient mice have increased bleeding times and are protected from collagen and adrenaline-induced thromboembolism. We conclude that G alpha(q) is essential for the signalling processes used by different platelet activators and that it cannot be replaced by G alpha(i) or the beta gamma subunits of the heterotrimeric G proteins. G alpha(q) may thus be a new target for drugs designed to block the activation of platelets.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena 91125, USA.
authors.forename: S
authors.initials: S
authors.lastname: Offermanns
authors.forename: C F
authors.initials: CF
authors.lastname: Toombs
authors.forename: Y H
authors.initials: YH
authors.lastname: Hu
authors.forename: M I
authors.initials: MI
authors.lastname: Simon
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006470:Hemorrhage / Q000209:etiology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction; D013923:Thromboembolism / Q000139:chemically induced; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium