KF31327, a new potent and selective inhibitor of cyclic nucleotide phosphodiesterase 5
KF31327, a new potent and selective inhibitor of cyclic nucleotide phosphodiesterase 5
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DOI：
10.1016/s0014-2999(01)01422-4
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发表时间：
2001-11-09
影响因子：
5
通讯作者：
Ichimura, M
中科院分区：
文献类型：
--
作者：
Hirose, R;Okumura, H;Ichimura, M
The effects of KF31327 (3-ethyl-8-[2-(4-hydroxymethylpiperidino)benzylamino]-2,3-dihydro-1 H -imidazo[4,5-g]quinazoline-2-thione dihydrochloride) on phosphodiesterase 5 (cyclic GMP-specific phosphodiesterase) activity and platelet aggregation were investigated and compared with those of sildenafil, a well-known phosphodiesterase 5 inhibitor. KF31327 inhibited phosphodiesterase 5 from canine trachea (K-i = 0.16 nM) more potently than sildenafil (K-i = 7.2 nM). The kinetic analysis revealed that KF31327 was a non-competitive inhibitor. In the presence of nitroglycerin (nitric oxide generator), both compounds inhibited the collagen-induced aggregation of rabbit platelets at less than 0.1 muM, augmenting intracellular cyclic GMP level without affecting cyclic AMP. In contrast, in the absence of nitroglycerin, a higher concentration (10 muM) of KF31327 was required to inhibit platelet aggregation and increased both cyclic nucleotide levels. However, 10 muM sildenafil did not affect aggregation despite elevation of cyclic GMP comparable to that in the presence of nitroglycerin, These results indicate that in the presence of nitroglycerin, the inhibition of platelet aggregation by KF31327 is due to the elevation of cyclic GMP, whereas the mechanism underlying the inhibition without nitroglycerin might be related to a rise in intracellular cyclic AMP. (C) 2001 Elsevier Science B.V. All rights reserved.
