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(Circulation Research. 2009;105:931.)
© 2009 American Heart Association, Inc.

Editorial

Controlling Myocyte cGMP

Phosphodiesterase 1 Joins the Fray

Eiki Takimoto

From the Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Md.

Correspondence to Eiki Takimoto, Division of Cardiology, Johns Hopkins Medical Institutions, 720 Rutland Ave, Ross 850, Baltimore, MD 21212. E-mail etakimo1@jhmi.edu

See related article, pages 956–964

Key Words: cGMP • phosphodiesterase • cardiac hypertrophy

An extract of the first 250 words of the full text is provided, because this article has no abstract.

CGMP is a central intracellular second-messenger regulating numerous cellular functions. In the cardiac myocyte, cGMP mediates effects of nitric oxide and atrial natriuretic peptide, whereas its counterpart, cAMP, mediates catecholamine signaling. Each cyclic nucleotide has a corresponding primary targeted protein kinase, protein kinase (PK)A for cAMP, and PKG for cGMP. PKA stimulation is associated with enhanced contractility and can stimulate growth, whereas PKG acts as a brake in the heart, capable of countering cAMP-PKA contractile stimulation and inhibiting hypertrophy.¹ Importantly, the duration and magnitude of these signaling cascades are determined not only by generation of cyclic nucleotides, but also by their hydrolysis catalyzed by phosphodiesterases (PDEs). PDE regulation is quite potent, often suppressing an acute rise in a given cyclic nucleotide back to baseline within seconds to minutes.² It is also compartmentalized within the cell, so that specific targeted proteins can be regulated by the same "generic" cyclic nucleotide.³ For many years, the only PDE in the crosshairs for cardiac biologists was PDE3, a principally cAMP-targeted PDE whose inhibition served as the basis for drugs such as milrinone as a heart failure therapy. However, this list was recently expanded with the recognition of PDE4 as a regulator of β-adrenergic signaling and excitation-contraction coupling,⁴ and PDE5 for its regulation of cardiac stress responses.¹ With the study of Miller et al,⁵ in this issue of Circulation Research, we can now add PDE1 to the list of hypertrophy regulators, via its modulation of cGMP in the myocyte.

The mammalian PDEs comprise a . . . [Full Text of this Article]

Related Article:

Role of Ca²⁺/Calmodulin-Stimulated Cyclic Nucleotide Phosphodiesterase 1 in Mediating Cardiomyocyte Hypertrophy

Clint L. Miller, Masayoshi Oikawa, Yujun Cai, Andrew P. Wojtovich, David J. Nagel, Xiangbin Xu, Haodong Xu, Vince Florio, Sergei D. Rybalkin, Joseph A. Beavo, Yiu-Fai Chen, Jian-Dong Li, Burns C. Blaxall, Jun-ichi Abe, and Chen Yan
Circ. Res. 2009 105: 956-964. [Abstract] [Full Text] [PDF]