ADP-INDUCED, PAF-INDUCED AND ADRENALINE-INDUCED PLATELET-AGGREGATION AND THROMBOXANE FORMATION ARE NOT AFFECTED BY A THROMBOXANE RECEPTOR ANTAGONIST AT PHYSIOLOGICAL EXTERNAL CA++ CONCENTRATIONS

被引:27
作者
BRETSCHNEIDER, E
GLUSA, E
SCHROR, K
机构
[1] UNIV DUSSELDORF,INST PHARMAKOL,D-40225 DUSSELDORF,GERMANY
[2] FORSCHUNGSZENTRUM VASK BIOL & MED ERFURT,D-99089 ERFURT,GERMANY
关键词
DALTROBAN; HIRUDIN; CITRATED PLASMA; THROMBOXANE; PLATELET SECRETION;
D O I
10.1016/0049-3848(94)90234-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thromboxane (TX) receptor antagonists are of considerable clinical interest in prevention of acute thrombembolic vessel occlusion. This study demonstrates that the selective TX receptor antagonist, daltroban, at a concentration (10 mu M) that does not inhibit TX synthesis, markedly inhibits ADP-, PAF- and adrenaline-induced platelet secretion and TX formation. With the exception of ADP-induced platelet secretion, these actions are only detectable in citrated platelet-rich plasma but not in plasma anticoagulated by hirudin. Since TX antagonists are supposed to act at physiological external Ca++ concentrations in the clinics, it is questionable whether in vitro studies in Ca++-deprived media are the optimum model to evaluate the clinical potential of these compounds.
引用
收藏
页码:233 / 242
页数:10
相关论文
共 29 条
[1]   AGGREGATION OF BLOOD PLATELETS BY ADENOSINE DIPHOSPHATE AND ITS REVERSAL [J].
BORN, GVR .
NATURE, 1962, 194 (4832) :927-&
[2]  
BRUGGENER E, 1991, N-S ARCH PHARMACOL, V343, pR44
[3]   INVITRO EFFECTS OF PICOTAMIDE ON HUMAN PLATELET-AGGREGATION, THE RELEASE REACTION AND THROMBOXANE-B2 PRODUCTION [J].
CATTANEO, M ;
TENCONI, PM ;
LECCHI, A ;
MANNUCCI, PM .
THROMBOSIS RESEARCH, 1991, 62 (06) :717-724
[4]   INTERRELATIONS OF PLATELET-AGGREGATION AND SECRETION [J].
CHARO, IF ;
FEINMAN, RD ;
DETWILER, TC .
JOURNAL OF CLINICAL INVESTIGATION, 1977, 60 (04) :866-873
[5]  
Fiddler G.I., 1990, CIRCULATION S1, V81, P69
[6]   ACTIVATION OF HUMAN-PLATELETS BY ADP CAUSES A RAPID RISE IN CYTOSOLIC FREE CALCIUM WITHOUT HYDROLYSIS OF PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE [J].
FISHER, GJ ;
BAKSHIAN, S ;
BALDASSARE, JJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1985, 129 (03) :958-964
[7]  
GLUSA E, 1990, HAEMOSTASIS, V20, P112
[8]  
GORDON JL, 1974, BRIT J PHARMACOL, V50, pP469
[9]  
HEPTINSTALL S, 1979, THROMB HAEMOSTASIS, V42, P778
[10]  
KERALY CL, 1988, THROMB HAEMOSTASIS, V60, P209