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tTwo isoforms of cGMP-inhibited cyclic nucleotide phosphodiesterases in human tissues distinguished by their responses to vesnarinone, a new cardiotonic agent.

                     
1993/01/29

Masuoka H, Ito M, Sugioka M, Kozeki H, Konishi T, Tanaka T, Nakano T.
Biochem Biophys Res Commun. 1993 Jan 29;190(2):412-7.

Abstract

We examined the inhibitory effects of vesnarinone, a new cardiotonic agent, on human cyclic nucleotide phosphodiesterase (PDE). Vesnarinone selectively inhibited the activity of human cardiac cGMP-inhibited PDE with a Ki value of 8.5 microM. The inhibition of human cardiac cGMP-inhibited PDE by vesnarinone was not competitive but was of the mixed type with respect to cAMP. Although the activities of the cGMP-inhibited PDE from human heart, aorta, platelets, and kidney were inhibited to the same extent by cGMP, enoximone, and cilostazole, vesnarinone inhibited the activities of cardiac and kidney cGMP-inhibited PDE with 10 times greater potency than those of platelet and aorta cGMP-inhibited PDE. These results suggest that there exist, in human tissues, two isoforms of cGMP-inhibited PDE that can be distinguished by reference to the inhibitory effects of vesnarinone.

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