1. Division of Biology 147-75, California Institute of Technology, Pasadena, California 91125, USA
2. Department of Pharmacology, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320, USA
3. Present address: Institut für Pharmakologie, Freie Universität Berlin, Thielallee 69–73, 14195 Berlin, Germany.

Correspondence to: Melvin I. Simon Correspondence and requests for materials should be addressed to M.I.S. (e-mail: Email: simonm@starbase1.caltech.edu).

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 haemostasis¹. Activation of platelets is also implicated in the pathogenesis of unstable angina, myocardial infarction and stroke²,³. Here we show that platelets from mice deficient in the -subunit of the heterotrimeric guanine-nucleotide-binding protein G_q are unresponsive to a variety of physiological platelet activators. As a result, G_q-deficient mice have increased bleeding times and are protected from collagen and adrenaline-induced thromboembolism. We conclude that G_q is essential for the signalling processes used by different platelet activators and that it cannot be replaced by G_i or the subunits of the heterotrimeric G proteins. G_q may thus be a new target for drugs designed to block the activation of platelets.