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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Takano, S. Ono, T. Kimura, J. |
Description | Author Affiliation: Takano S ( Department of Pharmacology, School of Medicine, Fukushima Medical University, Hikari-ga-oka 1, Fukushima 960-1295, Japan. s-takano@cc.fmu.ac.jp) |
Abstract | 1. We investigated the effect of KB-R7943, a Na(+)/Ca(2+) exchange inhibitor, on the aggregation response induced by adrenaline and 5-hydroxytryptamine (5-HT), alone or in combination in human and rabbit platelets in the presence or absence of ouabain. 2. KB-R7943 inhibited aggregation induced by the combination of adrenaline and 5-HT in a concentration-dependent manner. The IC(50) values of KB-R7943 were 4.2+/-2.0 or 3.0+/-0.7 microM with washed rabbit platelets with or without ouabain pretreatment, respectively. 3. In platelet-rich human plasma, the aggregation was biphasic. The IC(50) value of KB-R7943 was 17.2+/-4.4 microM for the first phase aggregation. 4. KB-R7943 did not inhibit the first phase of aggregation induced by adrenaline alone, or the monophasic aggregation induced by 5-HT alone. 5. The aggregation of rabbit platelets depended on the presence of K(+) in the medium, and K(+)-dependent and K(+)-independent Ca(2+) influx were observed in resting platelets. Ouabain treatment increased only the K(+)-dependent but not the K(+)-independent Ca(2+) influx. 6. KB-R7943 inhibited K(+)-dependent Ca(2+) influx with or without ouabain pretreatment, but not K(+)-independent Ca(2+) influx. 7. From these results, we conclude that KB-R7943 inhibits the adrenaline plus 5-HT induced aggregation of rabbit and human platelets by inhibiting K(+)-dependent Na(+)/Ca(2+) exchange (NCKX). Our results suggest that NCKX plays an important role in platelet aggregation. |
ISSN | 00071188 |
e-ISSN | 14765381 |
Journal | British Journal of Pharmacology |
Issue Number | 7 |
Volume Number | 132 |
Language | English |
Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
Publisher Date | 2001-04-01 |
Publisher Place | Great Britain (UK) |
Access Restriction | Open |
Subject Keyword | Blood Platelets Drug Effects Epinephrine Pharmacology Platelet Aggregation Serotonin Sodium-Calcium Exchanger Antagonists & Inhibitors Thiourea Analogs & Derivatives Animals Metabolism Calcium Calcium Radioisotopes Dose-Response Relationship, Drug Potassium Rabbits Time Factors Research Support, Non-U.S. Gov't |
Content Type | Text |
Resource Type | Article |
Subject | Pharmacology |
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