PMID: 9177254Jun 10, 1997Paper

Transgenic A1 adenosine receptor overexpression increases myocardial resistance to ischemia

Proceedings of the National Academy of Sciences of the United States of America
G Paul MatherneJohn P Headrick

Abstract

Activation of myocardial A1 adenosine receptors (A1AR) protects the heart from ischemic injury. In this study transgenic mice were created using the cardiac-specific alpha-myosin heavy chain promoter and rat A1AR cDNA. Heart membranes from two transgene positive lines displayed approximately 1,000-fold overexpression of A1AR (6,574 +/- 965 and 10,691 +/- 1,002 fmol per mg of protein vs. 8 +/- 5 fmol per mg of protein in control hearts). Compared with control hearts, transgenic Langendorff-perfused hearts had a significantly lower intrinsic heart rate (248 beats per min vs. 318 beats per min, P < 0. 05), lower developed tension (1.2 g vs. 1.6 g, P < 0.05), and similar coronary resistance. The difference in developed tension was eliminated by pacing. Injury of control hearts during global ischemia, indexed by time-to-ischemic contracture, was accelerated by blocking adenosine receptors with 50 microM 8-(p-sulfophenyl) theophylline but was unaffected by addition of 20 nM N6-cyclopentyladenosine, an A1AR agonist. Thus A1ARs in ischemic myocardium are presumably saturated by endogenous adenosine. Overexpressing myocardial A1ARs increased time-to-ischemic contracture and improved functional recovery during reperfusion. The data indic...Continue Reading

References

Mar 1, 1992·Circulation·S W Ely, R M Berne
Jul 1, 1989·Progress in Cardiovascular Diseases·L BelardinelliR M Berne
Oct 1, 1988·Pflügers Archiv : European journal of physiology·J Headrick, R J Willis
Jan 1, 1987·Naunyn-Schmiedeberg's Archives of Pharmacology·R F BrunsC C Huang
Apr 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·G M Church, W Gilbert
Apr 1, 1995·The Journal of Clinical Investigation·J C PlumierG N Pagoulatos
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·C HeurteauxM Lazdunski
Apr 1, 1993·Cardiovascular Research·C S Lawson, J M Downey
Jan 1, 1995·Biology of the Neonate·D L CothranG P Matherne
May 1, 1996·Cardiovascular Research·R S Vander Heide, K A Reimer
Jun 1, 1996·Journal of Molecular and Cellular Cardiology·J P Headrick
Aug 1, 1996·Journal of Molecular and Cellular Cardiology·T YoshidaD K Das

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Citations

Sep 25, 2004·Journal of Cellular Physiology·R YaarKatya Ravid
Apr 12, 2008·Purinergic Signalling·Andreas DeussenAnnette Pexa
Mar 12, 2004·Mechanisms of Ageing and Development·Tamsin L JennerRoselyn B Rose'Meyer
Apr 2, 2013·Trends in Molecular Medicine·Holger K EltzschigTobias Eckle
Jun 5, 2003·Experimental Neurology·Masatoshi YunokiKevin S Lee
Apr 2, 1999·Trends in Pharmacological Sciences·J W Nyce
Sep 17, 1999·Journal of Hepatology·O Le MoineJ Devière
May 16, 2000·Brain Research Bulletin·E Picano, M P Abbracchio
Nov 11, 1999·Drug Discovery Today·S M Kaiser, R J Quinn
Mar 7, 2006·Nature Reviews. Drug Discovery·Kenneth A Jacobson, Zhan-Guo Gao
Dec 22, 1999·British Journal of Pharmacology·J NeumannW Schmitz
Apr 1, 2000·Clinical and Experimental Pharmacology & Physiology·J P HeadrickG P Matherne
Jan 12, 2001·Clinical and Experimental Pharmacology & Physiology·R B Rose'MeyerR J Willis
Dec 4, 2010·Antioxidants & Redox Signaling·Almut GrenzHolger K Eltzschig
Sep 8, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ping YangJianfa Zhang
Dec 18, 2001·Journal of Cardiovascular Pharmacology·Jason PeartJohn P Headrick
Oct 12, 2010·Journal of Cardiovascular Pharmacology·Vijay B UrmaliyaPaul J White
Nov 6, 2010·Journal of Cardiovascular Pharmacology·Jun SasamoriKouichi Tanonaka
Apr 3, 2001·Annual Review of Neuroscience·T V Dunwiddie, S A Masino
Jul 14, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Habib R AnsariS Jamal Mustafa
May 4, 2012·American Journal of Physiology. Renal Physiology·H Sandeep PrakasamGerard Apodaca
Jul 27, 2002·Circulation Research·Richard G BlackJohn A Auchampach
Jun 30, 2009·Respiratory Research·Ashish K SharmaVictor E Laubach
Jun 1, 2010·BMC Developmental Biology·Christopher C WendlerScott A Rivkees
May 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Christopher C WendlerScott A Rivkees
Jun 15, 2013·Pharmacology & Therapeutics·John P HeadrickJason N Peart
May 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hiroshi IrieAzeddine Ibrahimi
Sep 29, 2011·Annual Review of Physiology·Sean P Colgan, Holger K Eltzschig
Oct 9, 2007·Journal of Molecular and Cellular Cardiology·Fadi N SalloumRakesh C Kukreja
May 12, 2007·Brain Research·Inmaculada IglesiasMairena Martín
Sep 4, 2008·Journal of Cellular Physiology·Cynthia St HilaireKatya Ravid
Sep 12, 2006·Cardiovascular Drug Reviews·Mervyn B FormanEdwin K Jackson

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