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Thromb Haemost 1998; 79(03): 614-619
DOI: 10.1055/s-0037-1614955
Review Articles
Schattauer GmbH

Inhibition of Rat Platelet Aggregation by Mycalolide-B, a Novel Inhibitor of Actin Polymerization with a Different Mechanism of Action from Cytochalasin-D

Atsuhiro Sugidachi
1   From the Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Department of Veterinary Pharmacology
,
Fumitoshi Asai
1   From the Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Department of Veterinary Pharmacology
,
Shinya Saito
1   From the Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Department of Veterinary Pharmacology
,
Hiroshi Ozaki
1   From the Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Department of Veterinary Pharmacology
,
Nobuhiro Fusetani
2   Department of Marine Biochemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan
,
Hideaki Karaki
1   From the Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Department of Veterinary Pharmacology
,
Hiroyuki Koike
1   From the Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Department of Veterinary Pharmacology
› Author Affiliations
Further Information

Publication History

Received 29 May 1997

Accepted after resubmission 09 November 1997

Publication Date:
07 December 2017 (online)

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Summary

In vitro effects of mycalolide-B (MB), isolated from marine sponge, were investigated with regard to the activation of rat platelets. Collagen-induced platelet aggregation in platelet-rich plasma (PRP) was slightly but significantly potentiated by lower concentrations of MB (0.3 and 1 μM) but was inhibited by higher concentrations (3 and 10 μM). ADP-induced platelet aggregation in PRP was also significantly prevented by MB (1-10 μM). Potentiation of ADP-induced aggregation by MB (0.3 μM) was hardly observed. G-actin contents, determined by DNase I inhibition assay, were increased in resting washed platelets incubated with MB (3 μM). In contrast, cytochalasin-D (CD) at 3 μM slightly reduced G-actin contents in resting platelets. After platelet aggregation with collagen (3 μg/ml) or ADP (10 μM), G-actin contents in platelets were reduced, indicating de novo actin polymerization. MB (3 μM) and CD (3 μM) abolished both ADP (10 μM)- and collagen (3 μg/ml)-induced platelet aggregation and actin polymerization in washed platelets. MB (1-10 μM) had no effects on intracellular Ca2+ concentrations in ADP (10 μM)-stimulated platelets. [125I]-fibrinogen binding to activated platelets with ADP (10 μM) was inhibited by MB (0.3-3 μM) in a concentration-dependent manner. Thrombin-induced platelet-fibrin clot retraction was inhibited by MB (1 and 10 μM). These results suggest that MB inhibits platelet activation by interfering with actin polymerization through a different mechanism of action from CD. MB may be a useful tool for studying the role of actin polymerization in various cells.

 

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