title: Impact of cigarette smoking on P2Y12 receptor binding activity before and after clopidogrel therapy in patients with coronary artery disease.
abstract: Smoking enhances the P2Y12 receptor inhibitory effects of clopidogrel. Nicotine increases P2Y12 receptor expression in platelet lysates from healthy volunteers. However, the impact of cigarette smoking on platelet P2Y12 receptor binding in clopidogrel-treated patients with coronary artery disease (CAD) is unknown. Clopidogrel-naïve patients with stable CAD (n = 20) were enrolled and stratified according to smoking status. P2Y12 receptor binding activity was determined by radioligand receptor binding prior and 24 h after a 600-mg loading dose of clopidogrel. Baseline P2Y12 receptor binding was 1.8-fold higher in smokers compared with nonsmokers. After a 600-mg loading dose of clopidogrel, smokers showed a 6.4-fold reduction in P2Y12 receptor binding indicative of marked clopidogrel-mediated blockade, while there were minimal changes among nonsmokers. Among patients with stable CAD, smokers have more P2Y12 receptor binding than nonsmokers and have a higher degree of clopidogrel-mediated platelet inhibition.
authors.affiliation: University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL, 32209, USA.
authors.forename: Jung Rae
authors.initials: JR
authors.lastname: Cho
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Haas
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.forename: Francesco
authors.initials: F
authors.lastname: Franchi
authors.forename: Ana
authors.initials: A
authors.lastname: Muñiz-Lozano
authors.forename: Antonio
authors.initials: A
authors.lastname: Tello-Montoliu
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferrante
authors.forename: Luis A
authors.initials: LA
authors.lastname: Guzman
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000627:therapeutic use*; D011869:Radioligand Assay; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects / Q000097:blood*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine