Antiplatelet effects of KW-7, a new inhibitor of cyclic nucleotide phosphodiesterases
| Autor: | Fang Rong Chang, Reen Yen Kuo, Chin Chung Wu, Yang Chang Wu, Wei Ya Wang |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Blood Platelets
medicine.medical_specialty Phosphodiesterase Inhibitors Thromboxane Cyclase Thromboxane Production Cyclic nucleotide chemistry.chemical_compound 3' 5'-Cyclic-GMP Phosphodiesterases Internal medicine medicine Animals Phosphodiesterase inhibitor Protein kinase A Pharmacology Sheep Dose-Response Relationship Drug biology Phosphodiesterase Isoquinolines Endocrinology chemistry 3' 5'-Cyclic-AMP Phosphodiesterases biology.protein Rabbits Thromboxane-A synthase Platelet Aggregation Inhibitors |
| Zdroj: | European Journal of Pharmacology. 483:187-194 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2003.10.046 |
| Popis: | The antiplatelet effect of a new synthetic compound, 8,9-dimethoxyl-1-(4-methoxy-phenyl)-5,6-dihydro-pyrrolo[2,1-a]isoquinoline-2,3-dione (KW-7), was determined in rabbit platelets. KW-7 concentration-dependently prevented platelet aggregation caused by arachidonic acid, collagen, platelet-activating factor, and thrombin. KW-7 induced a substantial increase in cyclic AMP levels and a smaller increase in cyclic GMP levels in platelets. In platelet homogenates, KW-7 inhibited both cyclic AMP- and cyclic GMP-phosphodiesterase activities. The antiplatelet effect of KW-7 was reversed by SQ22536 (an inhibitor of adenylate cyclase) and H89 (an inhibitor of protein kinase A) but not by ODQ (an inhibitor of soluble guanylate cyclase). These data suggest that the antiplatelet effect of KW-7 is cyclic AMP-dependent, and is through inhibition of platelet phosphodiesterases. In addition, KW-7 inhibited arachidonic acid-stimulated thromboxane production; this effect was associated with an increase in prostaglandin D2 levels indicating KW-7 is also an inhibitor of thromboxane synthase. The dual inhibition of KW-7 on phosphodiesterase and thromboxane synthase might provide an attractive target in developing antiplatelet drugs. |
| Databáze: | OpenAIRE |
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