The G protein coupled to the thromboxane A₂ receptor in human platelets is a member of the novel G_q family

The thromboxane A₂ (TXA₂) receptor in human platelets is coupled to a pertussis toxin-insensitive G protein whose identity has remained unknown. Candidates for this role include the atypical G protein known as G_z and members of a recently discovered G protein family known as G_q. Because of the proven utility of antibodies directed against the C terminus of G protein α subunits as functional probes, we prepared an antibody against a synthetic decapeptide corresponding to the C-terminal sequence shared by an and α_q, two members of the new family. This antibody (QL) does not recognize known a subunits but selectively binds to a 42-kDa protein in a variety of tissues, including human platelet membranes. QL and two other C-terminal antibodies, QN and AS, known to recognize α_z and α_i2, respectively, were tested for their ability to block agonist-stimulated GTPase activity in human platelet membranes. Pretreatment of platelet membranes with AS has previously been shown to interfere with α₂ adrenergic receptor-mediated inhibition of adenylylcyclase. As expected, only AS antibody produced inhibition of α₂ receptor-stimulated GTPase. Pretreatment of membranes with QL, but not QN or AS, caused marked inhibition of TXA₂ receptor-stimulated GTPase. This identifies the G protein coupled to human platelet TXA_z receptors as a member of the novel G_q family.