CAMP and cGMP signaling cross-talk - Role of phosphodiesterases and implications for cardiac pathophysiology

被引:279
作者
Zaccolo, Manuela
Movsesian, Matthew A.
机构
[1] Venetian Inst Mol Med, Dulbecco Telethon Inst, I-35129 Padua, Italy
[2] Vet Affairs Salt Lake City Hlth Care Syst, Cardiol Sect, Salt Lake City, UT USA
[3] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA
[4] Univ Utah, Sch Med, Dept Pharmacol, Salt Lake City, UT 84132 USA
关键词
phosphodiesterases; signaling cross-talk; cAMP; cGMP; compartmentalization;
D O I
10.1161/CIRCRESAHA.106.144501
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cyclic nucleotide phosphodiesterases regulate cAMP-mediated signaling by controlling intracellular cAMP content. The cAMP-hydrolyzing activity of several families of cyclic nucleotide phosphodiesterases found in human heart is regulated by cGMP. In the case of PDE2, this regulation primarily involves the allosteric stimulation of cAMP hydrolysis by cGMP. For PDE3, cGMP acts as a competitive inhibitor of cAMP hydrolysis. Several cGMP-mediated responses in cardiac cells, including a potentiation of Ca2+ currents and a diminution of the responsiveness to similar to beta-adrenergic receptor agonists, have been shown to result from the effects of cGMP on cAMP hydrolysis. These effects appear to be dependent on the specific spatial distribution of the cGMP-generating and cAMP-hydrolyzing proteins, as well as on the intracellular concentrations of the two cyclic nucleotides. Gaining a more precise understanding of how these cross-talk mechanisms are individually regulated and coordinated is an important direction for future research.
引用
收藏
页码:1569 / 1578
页数:10
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