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KMID : 0370019940080000017
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Chung-Ang Journal of Pharmacal Sciences
1994 Volume.8 No. 0 p.17 ~ p.26
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Anti-Platelet Aggregating Activity of 4,5-Dihydro-6-［3-nitro-4-methoxyphenyl］-5-methyl-3-［2H］-pyridazinone and Rolipram
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Shin Hwa-Woo
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Abstract
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The inhibitory effects of two types of phosphodiesterase(PDE) inhibitors(DMP and rolipram) on thrombin-stimulated platelet aggregation were investigated using rabbit platelets.
The effect of these PDE inhibitors on ATP secretion, intracellular Ca^2+ concentration and the contents of cAMP, cGMP, and IP_3 in the platelets were also studied in order to elucidate the action mechanisms of these PDE inhibitors.
50% Inhibitory concentrations(IC_50) of DMP and rolipram on aggregation were 2.21x10^-7 and 8.11x10^-4M, IC_50 of DMP and rolipram on ATP secretion were 2.01x10^-7, 7.35x10^-4, IC_50 of DMP and rolipram on intracellular Ca^2+ concentration were 2.21x10^-7 and 8.11x10^-4M, DMP sigificnatly increased cAMP content, but did not affect cGMP and IP_3 contents. Rolipram increased cGMP content significantly, but did not affect cAMP content.
These results suggest that the increased intracellular IP_3 content caused by thrombin-stimulated ATP release and thereby resulted in platelet aggregation. On the other hand, DMP, a new PDE Ⅲ inhibitor is believed to activate protein kinase A by increasing cAMP content and thereby either to release or store the intracellular free Ca^2+ concentration is believed to decrease ATP release and thereby to inhibit platelet aggregation.
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