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http://ir.cmu.edu.tw/ir/handle/310903500/22624
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| 題名: | Inhibitory Effects of nstpbp05250 on Cyclic Nucleotide Phosphodiesterase 5 |
| 作者: | 連金城(Lien,Jin-Cherng);侯曼貞(Hour,Mann-Jen);黃麗嬌(Huang,Li-Jiau);(吳俊昇);(陳柏舟);(吳宗翰);(黃德富);郭盛助(Kuo,Sheng-Chu) |
| 貢獻者: | 藥學院藥物化學研究所 |
| 日期: | 2006-08-23 |
| 上傳時間: | 2009-09-07 12:12:30 (UTC+8) |
| 摘要: | Cyclic nucleotides are major intracellular signaling molecules that play a crucial role in mammalian cells. Intracellular concentrations of cAMP or cGMP are regulated by their rate of formation via agonist-induced stimulation of adenylate cyclase or guanylate cyclase, and hydrolysis by a related group of phosphodiesterases (PDEs). The focus of the present paper is the cGMP-specific PDE5, which is a major cGMP-degrading enzyme. It is composed of 875 amino acids and expressed in various tissues such as the arterial vasculature, including coronary and pulmonary arteries, venous vasculature, skeletal muscles, platelets, visceral and tracheobronchial muscles, and lungs. PDE5 inhibitors have been reported to possess antiplatelet aggregation, weak cardiac inotropic effects and vascular relaxant properties. Owing to their causing smooth muscle relaxation in the corpus cavernosum, these PDE5 inhibitors have been approved for treatment of erectile dysfunction . Nstpbp05250, a pyrazole compound, exhibit significantly inhibitory effect against collagen and thrombin-induced platelet aggregation. Then it was demonstrated that nstpbp05250 itself markedly increased cyclic GMP level and potentiated the elevated cyclic GMP by nitroglycerin. Phosphodiesterase 5 was inhibited by nstpbp05250 with IC50, 4.21 μM. Nstpbp05250 significantly prolonged the latent period in triggering platelet plug formation in mesenteric venules of fluorescein sodium-pretreated mice, as it was intravenously given at a dose of 9 μg/g, whereas nstpbp05250 at the same dose had no significant effect on the tail bleeding time of mice. In conclusion, the promising antithrombotic profile of nstpbp05250 suggests that it is an attractive lead compound for developing antiplatelet drugs. |
| 關聯: | 2006年台灣藥學會藥物化學研討會 |
| 顯示於類別: | [藥物化學研究所] 會議論文
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