title: Antipsychotic Drugs Inhibit Platelet Aggregation via P2Y 1 and P2Y 12 Receptors.
abstract: Antipsychotic drugs (APDs) used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM). Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, and that clot firmness was decreased in platelets pretreated with APDs. We also examined the role two major adenosine diphosphate (ADP) receptors, P2Y1 and P2Y12, play in ADP-mediated platelet activation and APD-mediated suppression of platelet aggregation. Our results show that P2Y1 receptor stimulation with ADP-induced calcium influx was inhibited by APDs in human and rats' platelets, as assessed by in vitro or ex vivo approach, respectively. In contrast, APDs, risperidone and clozapine, alleviated P2Y12-mediated cAMP suppression, and the release of thromboxane A2 and arachidonic acid by activated platelets decreased after APD treatment in human and rats' platelets. Our data demonstrate that each APD tested significantly suppressed platelet aggregation via different mechanisms.
authors.affiliation: Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chang-Chieh
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City 231, Taiwan.
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Tsai
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City 231, Taiwan.
authors.forename: Mao-Liang
authors.initials: ML
authors.lastname: Chen
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City 231, Taiwan; Department of Life Science, Chinese Culture University, Shih Lin, Taipei 111, Taiwan.
authors.forename: Semon
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City 231, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi 600, Taiwan.
authors.forename: Tzung-Chieh
authors.initials: TC
authors.lastname: Tsai
authors.affiliation: Radiation Biology Core Laboratory, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan.
authors.forename: Lu-Kai
authors.initials: LK
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City 231, Taiwan.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism*; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12