Clinical and Molecular Genetics of the Phosphodiesterases (PDEs)

被引：251

作者：

Azevedo, Monalisa F. ^{[1
,2
]}

Faucz, Fabio R. ^{[1
,3
]}

Bimpaki, Eirini ^{[1
]}

Horvath, Anelia ^{[1
]}

Levy, Isaac ^{[1
]}

de Alexandre, Rodrigo B. ^{[1
,3
]}

Ahmad, Faiyaz ^{[4
]}

Manganiello, Vincent ^{[4
]}

Stratakis, Constantine A. ^{[1
,5
]}

机构：

[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA

[2] Univ Brasilia, Fac Med, Univ Hosp Brasilia, Endocrinol Sect, BR-70840901 Brasilia, DF, Brazil

[3] Pontificia Univ Catolica Parana, Sch Med, Grad Program Hlth Sci, Grp Adv Mol Invest, BR-80215901 Curitiba, Parana, Brazil

[4] NHLBI, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA

[5] NICHD, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA

来源：

ENDOCRINE REVIEWS | 2014年 / 35卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; CAMP-SPECIFIC PHOSPHODIESTERASE; PULMONARY ARTERIAL-HYPERTENSION; DEPENDENT PROTEIN-KINASE; CGMP-SPECIFIC PHOSPHODIESTERASE; ARYL-HYDROCARBON RECEPTOR; GMP-STIMULATED PHOSPHODIESTERASE; RECESSIVE RETINITIS-PIGMENTOSA; AMP-SPECIFIC PHOSPHODIESTERASE; STATIONARY NIGHT BLINDNESS;

D O I：

10.1210/er.2013-1053

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that have the unique function of terminating cyclic nucleotide signaling by catalyzing the hydrolysis of cAMP and GMP. They are critical regulators of the intracellular concentrations of cAMP and cGMP as well as of their signaling pathways and downstream biological effects. PDEs have been exploited pharmacologically for more than half a century, and some of the most successful drugs worldwide today affect PDE function. Recently, mutations in PDE genes have been identified as causative of certain human genetic diseases; even more recently, functional variants of PDE genes have been suggested to play a potential role in predisposition to tumors and/ or cancer, especially in cAMP-sensitive tissues. Mouse models have been developed that point to wide developmental effects of PDEs from heart function to reproduction, to tumors, and beyond. This review brings together knowledge from a variety of disciplines (biochemistry and pharmacology, oncology, endocrinology, and reproductive sciences) with emphasis on recent research on PDEs, how PDEs affect cAMP and cGMP signaling in health and disease, and what pharmacological exploitations of PDEs may be useful in modulating cyclic nucleotide signaling in a way that prevents or treats certain human diseases.

引用

页码：195 / 233

页数：39

共 483 条

[91] 1,5-Substituted nipecotic amides: Selective PDE8 inhibitors displaying diastereomer-dependent microsomal stability [J].