title: Effect of serotonin on platelet function in cocaine exposed blood.
abstract: 5-hydroxytryptamine (5-HT) reuptake inhibitors counteract the pro-thrombotic effect of elevated plasma 5-HT by down-regulating the 5-HT uptake rates of platelets. Cocaine also down-regulates the platelet 5-HT uptake rates but in contrast, the platelets of cocaine-injected mice show a much higher aggregation rate than the platelets of control mice. To examine the involvement of plasma 5-HT in cocaine-mediated platelet aggregation, we studied the function of platelets isolated from wild-type and transgenic, peripheral 5-HT knock-out (TPH1-KO) mice, and cocaine-insensitive dopamine transporter knock in (DAT-KI) mice. In cocaine-injected mice compared to the control mice, the plasma 5-HT level as well as the surface level of P-selectin was elevated; in vitro platelet aggregation in the presence of type I fibrillar collagen was enhanced. However, cocaine injection lowered the 5-HT uptake rates of platelets and increased the plasma 5-HT levels of the DAT-KI mice but did not change their platelets aggregation rates further which are already hyper-reactive. Furthermore, the in vitro studies supporting these in vivo findings suggest that cocaine mimics the effect of elevated plasma 5-HT level on platelets and in 5-HT receptor- and transporter-dependent pathways in a two-step process propagates platelet aggregation by an additive effect of 5-HT and nonserotonergic catecholamine.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences.
authors.forename: Endrit
authors.initials: E
authors.lastname: Ziu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences.
authors.forename: Coedy
authors.initials: C
authors.lastname: Hadden
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences.
authors.forename: Yicong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences.
authors.forename: Curtis Lee
authors.initials: CL
authors.lastname: Lowery
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences.
authors.forename: Preeti
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences.
authors.forename: Serra S
authors.initials: SS
authors.lastname: Ucer
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Mercado
authors.affiliation: Department of Pharmacology, College of Medicine, Ohio State University.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Gu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences.
authors.forename: Fusun
authors.initials: F
authors.lastname: Kilic
mesh_terms: D000818:Animals; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D015283:Citalopram / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D055879:Gene Knock-In Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000172:deficiency / Q000235:genetics; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D015283:Citalopram; D003042:Cocaine; D024042:Collagen Type I; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D019007:P-Selectin; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors
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