Inhibitory mechanisms of dantrolene on platelet aggregation

被引：10

作者：

Chou, TC ^{[1
]}

Li, CY ^{[1
]}

机构：

[1] Natl Def Med Ctr, Tri Serv Gen Hosp, Grad Inst Med Sci, Dept Med Res, Taipei, Taiwan

来源：

THROMBOSIS RESEARCH | 1999年 / 96卷 / 04期

关键词：

dantrolene; platelet aggregation; thromboxane B-2; phosphoinositide breakdown;

D O I：

10.1016/S0049-3848(99)00114-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The antiplatelet effect of dantrolene and possible inhibitory mechanisms were studied in rabbit platelets. Preincubation of rabbit washed platelets with dantrolene (50-300 mu M) inhibited the platelet aggregation and adenosine triphosphate release induced by arachidonic acid (100 mu M), collagen (10 mu g/mL), or thrombin (0.1 U/mL) in a dose-dependent manner. The thromboxane B-2 formation caused by collagen or thrombin was inhibited by dantrolene, while formation of thromboxane B-2 and prostaglandin D-2 induced by arachidonic acid were not inhibited. In addition, the formation of phosphoinositide breakdown and the rise of intracellular calcium level induced by collagen or thrombin were also inhibited in a dose-dependent manner by dantrolene in the presence of indomethacin (2 mu M). However, the platelets cyclic AMP level was not affected by dantrolene, In conclusion, the present study demonstrates that dantrolene inhibits platelet activation mainly due to suppression of phosphoinositide breakdown. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：299 / 307

页数：9

共 30 条

[11] THROMBOXANES - NEW GROUP OF BIOLOGICALLY-ACTIVE COMPOUNDS DERIVED FROM PROSTAGLANDIN ENDOPEROXIDES [J].

HAMBERG, M ;

SVENSSON, J ;

SAMUELSSON, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1975, 72 (08) :2994-2998

[12] EVIDENCE THAT PROSTAGLANDIN ENDOPEROXIDES CAN INDUCE PLATELET-AGGREGATION IN THE ABSENCE OF THROMBOXANE A2 PRODUCTION [J].

HORNBY, EJ ;

SKIDMORE, IF .

BIOCHEMICAL PHARMACOLOGY, 1982, 31 (06) :1158-1160

[13] PROSTAGLANDINS - SPECIFIC-INHIBITION OF PLATELET-ADHESION TO COLLAGEN AND RELATIONSHIP WITH CAMP LEVEL [J].

KARNIGUIAN, A ;

LEGRAND, YJ ;

CAEN, JP .

PROSTAGLANDINS, 1982, 23 (04) :437-454

[14]

KIRK C J, 1981, Biochemical Society Transactions, V9, P377

[15]

KROLL MC, 1989, BLOOD, V74, P1185

[16] MYOINOSITOL 1,4,5-TRISPHOSPHATE STIMULATES PROTEIN-PHOSPHORYLATION IN SAPONIN-PERMEABILIZED HUMAN-PLATELETS [J].

LAPETINA, EG ;

WATSON, SP ;

CUATRECASAS, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (23) :7431-7435

[17] EFFECTS OF DANTROLENE ON MYOPLASMIC FREE [CA2+] MEASURED INVIVO IN PATIENTS SUSCEPTIBLE TO MALIGNANT HYPERTHERMIA [J].

LOPEZ, JR ;

GERARDI, A ;

LOPEZ, MJ ;

ALLEN, PD .

ANESTHESIOLOGY, 1992, 76 (05) :711-719

[18]

MACINTYRE DE, 1985, ADV EXP MED BIOL, V192, P127

[19]

MASSINI P, 1981, BIOCHIM BIOPHYS ACTA, V21, P523

[20]

Mustard J F, 1976, Trans Am Clin Climatol Assoc, V87, P104

← 1 2 3 →