Internal medicine

Autocrine signalling

G protein-coupled receptor

Receptor

Enzyme

Atrial natriuretic peptide

Heart failure

Contractility

Phosphodiesterase

Gq alpha subunit

Biology

Endocrinology

Second messenger system

Chemistry

Natriuretic peptide

Phosphodiesterase 3

Signal transduction

PDE10A

Cell biology

Biochemistry

Medicine

Paracrine signalling

Intracellular

International Journal of Molecular Sciences

Cardiac contractility is regulated by several neural, hormonal, paracrine, and autocrine factors. Amongst these, signaling through β-adrenergic and serotonin receptors generates the second messenger cyclic AMP (cAMP), whereas activation of natriuretic peptide receptors and soluble guanylyl cyclases generates cyclic GMP (cGMP). Both cyclic nucleotides regulate cardiac contractility through several mechanisms. Phosphodiesterases (PDEs) are enzymes that degrade cAMP and cGMP and therefore determine the dynamics of their downstream effects. In addition, the intracellular localization of the different PDEs may contribute to regulation of compartmented signaling of cAMP and cGMP. In this review, we will focus on the role of PDEs in regulating contractility and evaluate changes in heart failure.

Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts