ACTIVATION OF HUMAN PLATELETS BY COCAINE

被引:106
作者
KUGELMASS, AD
ODA, A
MONAHAN, K
CABRAL, C
WARE, JA
机构
[1] BETH ISRAEL HOSP, DEPT MED,DIV CARDIOVASC,HARVARD THORNDIKE LAB, 330 BROOKLINE AVE, BOSTON, MA 02215 USA
[2] CHARLES A DANA RES INST, BOSTON, MA USA
[3] BETH ISRAEL HOSP, DEPT SURG, BOSTON, MA 02215 USA
[4] HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA
关键词
COCAINE; THROMBOSIS; PLATELETS; P-SELECTIN; FIBRINOGEN;
D O I
10.1161/01.CIR.88.3.876
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background. Cocaine ingestion has been associated with thrombosis of coronary as well as peripheral arteries, but the mechanism by which cocaine promotes thrombus formation is unknown. Accordingly, we determined whether cocaine activates human platelets by flow cytometric analysis of whole blood to which cocaine was added. Methods and Results. Activated platelets were detected by two-color'' flow cytometric analysis of the binding of fluorescently labeled antibodies directed against either platelet-associated fibrinogen or P-selectin, which are found on the surface of platelets only after stimulation. Platelets were distinguished from other constituents of whole blood by their ability to bind an anti-glycoprotein Ib antibody bound to both activated and resting platelets. Incubation of whole blood with cocaine, in concentrations of 10 muM to 13 mM, induced significant increases in both platelet-associated fibrinogen (range of increase, 45+/-12% to 125+/-40%) and P-selectin expression (36+/-15% to 112+/-24%). In platelets suspended in either buffer or plasma, however, P-selectin expression was detected only at the highest cocaine concentration (85+/-13% increase in plasma and 59+/-7% in buffer). Neither aspirin nor the ADP scavenger apyrase inhibited cocaine-induced P-selectin expression. Cocaine inhibited the uptake of C-14-radiolabeled serotonin by platelets (IC50, 8.7 muM). P-selectin expression and fibrinogen binding were found after the addition of cocaine alone to blood taken from some but not all donors; however, platelet activation in response to submaximal concentrations of the agonists ADP or epinephrine was enhanced by a low concentration of cocaine added to blood from every donor. Conclusions. Cocaine, in concentrations similar to those found clinically, induces activation of individual platelets studied in whole blood from some but not all donors, and platelet response to physiological agonists is enhanced by cocaine. Thus, cocaine-induced platelet activation may contribute to thrombosis following cocaine ingestion.
引用
收藏
页码:876 / 883
页数:8
相关论文
共 49 条
[1]   MECHANISM OF ETHANOL-INDUCED AGGREGATION IN WHOLE-BLOOD [J].
ABIYOUNES, SA ;
AYERS, ML ;
MYERS, AK .
THROMBOSIS RESEARCH, 1991, 63 (05) :481-489
[2]   EFFECTS OF KETANSERIN AND MEPYRAMINE ON PLATELET-AGGREGATION AND ON THE UPTAKE OF 5-HYDROXYTRYPTAMINE INTO PLATELETS [J].
BEVAN, J ;
HEPTINSTALL, S .
THROMBOSIS RESEARCH, 1983, 30 (05) :415-423
[3]  
BEVILACQUA M, 1991, CELL, V67, P223
[4]  
CHIUEH CC, 1978, J PHARMACOL EXP THER, V205, P148
[5]  
COLLER BS, 1983, BLOOD, V61, P99
[6]   PULMONARY INFARCTION ASSOCIATED WITH CRACK COCAINE USE IN A PREVIOUSLY HEALTHY 23-YEAR-OLD WOMAN [J].
DELANEY, K ;
HOFFMAN, RS .
AMERICAN JOURNAL OF MEDICINE, 1991, 91 (01) :92-94
[7]   QUANTITATIVE-ANALYSIS OF AMOUNTS OF CORONARY ARTERIAL NARROWING IN COCAINE ADDICTS [J].
DRESSLER, FA ;
MALEKZADEH, S ;
ROBERTS, WC .
AMERICAN JOURNAL OF CARDIOLOGY, 1990, 65 (05) :303-308
[8]  
FEINSTEIN MB, 1976, J PHARMACOL EXP THER, V197, P215
[9]   PLATELET SURFACE GLYCOPROTEINS - STUDIES ON RESTING AND ACTIVATED PLATELETS AND PLATELET MEMBRANE MICROPARTICLES IN NORMAL SUBJECTS, AND OBSERVATIONS IN PATIENTS DURING ADULT RESPIRATORY-DISTRESS SYNDROME AND CARDIAC-SURGERY [J].
GEORGE, JN ;
PICKETT, EB ;
SAUCERMAN, S ;
MCEVER, RP ;
KUNICKI, TJ ;
KIEFFER, N ;
NEWMAN, PJ .
JOURNAL OF CLINICAL INVESTIGATION, 1986, 78 (02) :340-348
[10]   THE EFFECTS OF LOCAL-ANESTHETICS ON MATERNAL AND NEONATAL PLATELET-FUNCTION [J].
GRANT, GJ ;
RAMANATHAN, S ;
PATEL, N ;
TURNDORF, H .
ACTA ANAESTHESIOLOGICA SCANDINAVICA, 1989, 33 (05) :409-412