Desensitization of NO/cGMP signaling in smooth muscle: blood vessels versus airways

Molecular Pharmacology
Florian MullershausenDoris Koesling

Abstract

The NO/cGMP signaling pathway plays a major role in the cardiovascular system, in which it is involved in the regulation of smooth muscle tone and inhibition of platelet aggregation. Under pathophysiological conditions such as endothelial dysfunction, coronary artery disease, and airway hyperreactivity, smooth muscle containing arteries and bronchi are of great pharmacological interest. In these tissues, NO mediates its effects by stimulating guanylyl cyclase (GC) to form cGMP; the subsequent increase in cGMP is counteracted by the cGMP-specific phosphodiesterase (PDE5), which hydrolyzes cGMP. In platelets, allosteric activation of PDE5 by cGMP paralleled by phosphorylation has been shown to govern the sensitivity of NO/cGMP signaling. Here, we demonstrate that the functional responsiveness to NO correlates with the relative abundance of GC and PDE5 in aortic and bronchial tissue, respectively. We show a sustained desensitization of the NO-induced relaxation of aortic and bronchial rings caused by a short-term exposure to NO. The NO treatment caused heterologous desensitization of atrial natriuretic peptide-induced relaxation, whereas relaxation by the cGMP analog 8-pCPT-cGMP was unperturbed. Impaired relaxation was shown to be...Continue Reading

References

Jun 26, 1998·The EMBO Journal·A PfeiferF Hofmann
Feb 5, 1999·Reviews of Physiology, Biochemistry and Pharmacology·D M JuilfsJ A Beavo
Feb 5, 1999·Reviews of Physiology, Biochemistry and Pharmacology·A PfeiferF Hofmann
Feb 5, 1999·Reviews of Physiology, Biochemistry and Pharmacology·M BielF Hofmann
Apr 20, 1999·The Journal of Experimental Medicine·S MassbergF Hofmann
Dec 10, 1999·American Journal of Respiratory and Critical Care Medicine·M KakuyamaP Vallance
Apr 5, 2001·American Journal of Physiology. Cell Physiology·T Welbourne, I Nissim
Nov 28, 2001·The Journal of Biological Chemistry·Sergei D RybalkinJoseph A Beavo
Jan 30, 2003·The EMBO Journal·Sergei D RybalkinJoseph A Beavo
Feb 27, 2003·The Journal of Cell Biology·Florian MullershausenDoris Koesling
Nov 18, 2005·Methods in Enzymology·Michael Russwurm, Doris Koesling

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Citations

Jan 31, 2009·Nature Reviews. Drug Discovery·Jia JiaYu Zong Chen
Dec 8, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andrew M BatchelorJohn Garthwaite
Aug 19, 2010·Pharmacological Reviews·Sharron H FrancisDavid Sibley
Dec 29, 2010·Pulmonary Pharmacology & Therapeutics·Mehdi OualhaChristophe Delclaux
Jul 1, 2008·The European Journal of Neuroscience·John Garthwaite
Jun 15, 2013·British Journal of Pharmacology·Barbara LiesAndreas Friebe
Feb 13, 2010·Journal of Thrombosis and Haemostasis : JTH·O DangelA Friebe
Jul 16, 2009·Nitric Oxide : Biology and Chemistry·Catherine N Hall, John Garthwaite
Jun 25, 2014·Burns : Journal of the International Society for Burn Injuries·O GoertzJ Kolbenschlag
Jul 23, 2016·International Journal of Cardiology·Luigino CalzettaMaria Gabriella Matera
Jul 25, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Christian KrawutschkeMichael Russwurm
Nov 7, 2018·British Journal of Pharmacology·John Garthwaite
Mar 27, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·William J PerkinsKeith A Jones
May 23, 2007·The Biochemical Journal·Michael RusswurmDoris Koesling
Jul 28, 2020·PLoS Computational Biology·William Davis HaseldenPatrick J Drew
Nov 19, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Masahiro EnomotoJaques Belik
Sep 11, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Berat KrasniqiMentor Sopjani

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