title: Coactivation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation.
abstract: ADP is an important platelet agonist causing shape change and aggregation required for physiological hemostasis. We recently demonstrated the existence of two distinct G protein-coupled ADP receptors on platelets, one coupled to phospholipase C, P2Y1, and the other to inhibition of adenylyl cyclase, P2TAC. In this study, using specific antagonists for these two receptors, we demonstrated that concomitant intracellular signaling from both the P2TAC and P2Y1 receptors is essential for ADP-induced platelet aggregation. Inhibition of signaling through either receptor, by specific antagonists, is sufficient to block ADP-induced platelet aggregation. Furthermore, signaling through the P2TAC receptor could be replaced by activation of alpha2A-adrenergic receptors. On the other hand, activation of serotonin receptors supplements signaling through the P2Y1 receptor. Moreover, this mechanism of ADP-induced platelet aggregation could be mimicked by coactivation of two non-ADP receptors coupled to Gi and Gq, neither of which can cause platelet aggregation by itself. We propose that platelet aggregation results from concomitant signaling from both the Gi and Gq, a mechanism by which G protein-coupled receptors elicit a physiological response.
authors.affiliation: Department of Physiology, Temple University Medical School, Philadelphia, PA 19140, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.forename: S P
authors.initials: SP
authors.lastname: Kunapuli
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D000244:Adenosine Diphosphate; D019204:GTP-Binding Proteins