The AMP-Dependent Protein Kinase (AMPK) Activator A-769662 Causes Arterial Relaxation by Reducing Cytosolic Free Calcium Independently of an Increase in AMPK Phosphorylation

Frontiers in Pharmacology
Yi HuangP H Ratz

Abstract

Although recent studies reveal that activation of the metabolic and Ca(2+) sensor AMPK strongly inhibits smooth muscle contraction, there is a paucity of information about the potential linkage between pharmacological AMPK activation and vascular smooth muscle (VSM) contraction regulation. Our aim was to test the general hypothesis that the allosteric AMPK activator A-769662 causes VSM relaxation via inhibition of contractile protein activation, and to specifically determine which activation mechanism(s) is(are) affected. The ability of A-769662 to cause endothelium-independent relaxation of contractions induced by several contractile stimuli was examined in large and small musculocutaneous and visceral rabbit arteries. For comparison, the structurally dissimilar AMPK activators MET, SIM, and BBR were assessed. A-769662 displayed artery- and agonist-dependent differential inhibitory activities that depended on artery size and location. A-769662 did not increase AMPK-pT172 levels, but did increase phosphorylation of the downstream AMPK substrate, acetyl-CoA carboxylase (ACC). A-769662 did not inhibit basal phosphorylation levels of several contractile protein regulatory proteins, and did not alter the activation state of rhoA. A...Continue Reading

References

Mar 29, 2001·European Journal of Pharmacology·M Alvarez de SotomayorE Marhuenda
Sep 13, 2003·Pharmacology & Toxicology·Andreas BergdahlKarl Swärd
Jun 17, 2004·Molecular and Cellular Biology·Catrin A PritchardJim C Norman
Sep 21, 2004·Journal of Applied Physiology·L J RubinC C Hale
Nov 23, 2006·Circulation·Wei SunJohn Y-J Shyy
Apr 21, 2007·The Journal of Physiology·Françoise GoirandAnne Garnier
Sep 15, 2007·The Journal of Biological Chemistry·Olga GöranssonKei Sakamoto
Apr 23, 2008·The Journal of Biological Chemistry·Sandrine HormanMark H Rider
Jul 11, 2008·Progress in Biophysics and Molecular Biology·Christelle GuibertJean-Pierre Savineau
Dec 10, 2009·Physiology·Sandra PuetzGabriele Pfitzer
Oct 26, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Rebecca J Ford, James W E Rush
Nov 30, 2010·Pharmacology & Therapeutics·Marie-Ann Ewart, Simon Kennedy
Jan 1, 2008·Advances in Pharmacological Sciences·Yan-Ping DaiIlia A Yamboliev
Jun 28, 2011·Journal of Muscle Research and Cell Motility·Lyndsay J ClellandPaul H Ratz
Aug 20, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Marion GayardMalvyne Rolli-Derkinderen
Jan 16, 2014·American Journal of Physiology. Endocrinology and Metabolism·Serge DucommunKei Sakamoto
Apr 22, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Aurélie D TimmermansLuc Bertrand
May 27, 2014·Chemistry & Biology·Benoit ViolletUwe Schlattner
Feb 6, 2017·Current Vascular Pharmacology·Guilherme Henrique Souza BomfimNeide Hyppolito Jurkiewicz

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Citations

Nov 2, 2019·Basic & Clinical Pharmacology & Toxicology·Hui ChenSusan Wai Sum Leung
Sep 16, 2018·International Journal of Molecular Sciences·Nina ZippelBeate Fisslthaler
Dec 20, 2018·International Journal of Molecular Sciences·Anastasiya StrembitskaIan P Salt
May 28, 2020·Frontiers in Pharmacology·Mingying DengAizong Shen
Nov 22, 2018·Cell Communication and Signaling : CCS·Ponarulselvam SekarWan-Wan Lin
Feb 3, 2021·European Journal of Pharmacology·Mohammed SaartiRichard E Roberts

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

Graph Pad Prism
Felix
GraphPad

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