Distinct phosphodiesterase 5A-containing compartments allow selective regulation of cGMP-dependent signalling in human arterial smooth muscle cells

Cellular Signalling
Lindsay S WilsonD H Maurice

Abstract

Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO·) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca2+ in human platelets. Herein, we report that PDE5A integrates into an analogous signalosome in human arterial smooth muscle cells (HASMC), wherein it regulates muscarinic agonist-dependent Ca2+ release and is activated selectively by PKG-dependent phosphorylation. In addition, we report that PDE5A also regulates HASMC functions via events independent of PKG, but rather through actions coordinated by competitive cGMP-mediated inhibition of cAMP hydrolysis by the so-called cGMP-inhibited cAMP PDE, namely phosphodiesterase 3A (PDE3A). Indeed, we show that ANP increases both cGMP and cAMP levels in HASMC and promotes phosphorylation of vasodilator-stimulated phospho-protein (VASP) at each t...Continue Reading

Citations

Mar 3, 2019·British Journal of Pharmacology·Liang ZhangVéronique Leblais
Nov 20, 2018·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·Ji-Sheng WangBin Wang
Jun 30, 2019·International Journal of Molecular Sciences·Jheelam BanerjeeMichael B Zemel

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