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(Circulation Research. 2007;100:309.)
© 2007 American Heart Association, Inc.

Reviews

Overview of PDEs and Their Regulation

Kenji Omori, Jun Kotera

From the Discovery Research Laboratories, Tanabe Seiyaku Co Ltd, Saitama, Japan.

Correspondence to Kenji Omori, Discovery Research Laboratories, Tanabe Seiyaku Co Ltd, 2-50 Kawagishi 2-chome, Toda, Saitama 335-8505, Japan. E-mail k-omori{at}tanabe.co.jp

This Review is part of a thematic series on Phosphodiesterases, which includes the following articles:

Compartmentation of Cyclic Nucleotide Signaling in the Heart: The Role of Cyclic

Nucleotide Phosphodiesterases

Overview of PDEs and Their Regulation

Regulation of Phosphodiesterase 3 (PDE3) and Inducible cAMP Early Repressor (ICER) in the Heart

cAMP and cGMP Signaling Cross-Talk: Role of Phosphodiesterases and Implications for Cardiac Pathophysiology

cAMP Specific Phosphodiesterase-4 Enzymes in the Cardiovascular System: A

Molecular Toolbox for Generating Compartmentalized cAMP Signalling PDE5
David A. Kass Editor

Contraction and relaxation of vascular smooth muscle and cardiac myocytes are key physiological events in the cardiovascular system. These events are regulated by second messengers, cAMP and cGMP, in response to extracellular stimulants. The strength of signal transduction is controlled by intracellular cyclic nucleotide concentrations, which are determined by a balance in production and degradation of cAMP and cGMP. Degradation of cyclic nucleotides is catalyzed by 3',5'-cyclic nucleotide phosphodiesterases (PDEs), and therefore regulation of PDEs hydrolytic activity is important for modulation of cellular functions. Mammalian PDEs are composed of 21 genes and are categorized into 11 families based on sequence homology, enzymatic properties, and sensitivity to inhibitors. PDE families contain many splice variants that mostly are unique in tissue-expression patterns, gene regulation, enzymatic regulation by phosphorylation and regulatory proteins, subcellular localization, and interaction with association proteins. Each unique variant is closely related to the regulation of a specific cellular signaling. Thus, multiple PDEs function as a particular modulator of each cardiovascular function and regulate physiological homeostasis.

Key Words: cAMP • cGMP • cyclic nucleotide • cell signaling • phosphodiesterase inhibitor

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