ROLE OF CYCLIC-AMP IN ADENOSINE INHIBITION OF INTRACELLULAR CALCIUM RISE IN HUMAN PLATELETS - COMPARISON OF ADENOSINE EFFECTS ON THROMBIN-INDUCED AND EPINEPHRINE-INDUCED PLATELET STIMULATION

被引:12
作者
FEOKTISTOV, IA
PAUL, S
HOLLISTER, AS
ROBERTSON, D
BIAGGIONI, I
机构
[1] Institute of Cardiology, Tomsk
[2] Departments of Medicine and Pharmacology, Division of Clinical Pharmacology and the Clinical Research Center, Vanderbilt University, Nashville, TN
关键词
ADENOSINE; THROMBIN; EPINEPHRINE; CYCLIC AMP; HUMAN PLATELETS; INTRACELLULAR CALCIUM;
D O I
10.1093/ajh/5.6.147S
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Thrombin-induced platelet aggregation is associated with an increase in intracellular calcium. Epinephrine provokes aggregation in the absence of a rise in intracellular calcium. Adenosine has been postulated as an endogenous inhibitor of platelet aggregation. In this study, the authors examine the effect of adenosine on the rise in intracellular calcium and on platelet aggregation, and the role of cyclic AMP (cAMP) in these actions. Human platelets were obtained from citrated plasma containing 5-mu-g/mL of indomethacin. Intracellular calcium was determined by fura-2 fluorescent dye. Adenosine inhibited thrombin-induced platelet aggregation and the rise in intracellular calcium in a dose-dependent manner. At a concentration of 100-mu-mol/L, adenosine completely inhibited thrombin-induced aggregation, but only partly inhibited the rise in intracellular calcium (55%). Adenosine also partially inhibited the rise in calcium produced by thrombin in both calcium-containing and calcium-free media, suggesting that adenosine inhibits both calcium influx and calcium mobilization. The effects of adenosine on intracellular calcium, as in the case of platelet aggregation, appear to be linked to adenylate cyclase, since they were prevented by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine (1-mmol/L) and were potentiated by phosphodiesterase inhibition with papaverine (1-mu-mol/L). Adenosine and dibutyryl-cAMP also inhibited epinephrine-stimulated platelet aggregation in a dose-dependent manner. Thus, it appears that adenosine may inhibit platelet aggregation independently of its ability to decrease cytosolic free calcium.
引用
收藏
页码:S147 / S153
页数:7
相关论文
共 30 条
[1]  
Siess W., Molecular mechanisms of platelet activation, Physiol Rev, 69, pp. 58-178, (1989)
[2]  
Rittenhouse-Simmons S., Differential activation of platelet phospholipases by thrombin and ionophore A23187, J Biol Chem, 256, pp. 4153-4155, (1981)
[3]  
Rao G., Peller J.D., White J.G., Measurement of ionized calcium in blood platelets with a new generation calcium indicator, Biochem Biophys Res Commun, 132, pp. 652-657, (1985)
[4]  
Clare K.A., Scrutton M.C., Thompson N.T., Effects of alpha- 2 adrenoreceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets, Br J Pharmacol, 82, pp. 467-476, (1984)
[5]  
Thompson N.T., Scrutton M.C., Intracellular calcium fluxes in human platelets, Eur J Biochem, 147, pp. 421-427, (1985)
[6]  
Siess W., Lapetina E.G., CA2+-Mobilization primes protein kinase C in human platelets. Ca2+and phorbol ester stimulate platelet aggregation and secretion synergistically through protein kinase C, Biochem J, 255, pp. 309-318, (1988)
[7]  
Baldenkov G.N., Negrescu E.V., Mazaev A.V., Et al., Synergism in hormonal actions on intracellular calcium level in human platelets (In Russian), Dokl Akad Nauk USSR, 296, pp. 1015-1017, (1987)
[8]  
Stiles G.L., Adenosine receptors: Structure, function and regulation, Trends Pharmacol Sci, 7, pp. 486-490, (1986)
[9]  
Gerlach E., Becker B.F., Nees S., Formation of adenosine by vascular endothelium: A homeostatic and antithrombo- genic mechanism?, Topics and Perspectives in Adenosine Research, pp. 309-320, (1987)
[10]  
Dawicki D.D., Agarwal K.C., Parks R.E., Potentiation of the antiplatelet action of adenosine in whole blood by dipiridamole or dilazep and cAMP phosphodiesterase inhibitor, RA 233, Thromb Res, 43, pp. 161-175, (1986)