title: Adenosine receptor blockade enhance glycolysis in hypoperfused guinea-pig myocardium.
abstract: OBJECTIVE
  This study tested the hypothesis that endogenous adenosine depresses anaerobic glycolysis in preischaemic and moderately ischaemic myocardium.
  
  
  METHODS
  Isolated, working guinea-pig hearts, perfused with glucose-fortified Krebs-Henseleit buffer, were subjected to 15 min mild hypoperfusion (coronary flow 60% of baseline) followed by 10 min ischaemia (coronary flow 20% of baseline). Adenosine A1 receptors were blocked with 8-p-sulfophenyl theophylline (8-SPT; 20 microM). Glucose oxidation and lactate production from exogenous glucose were assessed from 14CO2 and [14C]lactate formation, respectively, from [U-14C]glucose. Energy metabolites, glycolytic intermediates and glycogen were measured in extracts of stop-frozen preischaemic, mildly hypoperfused and ischaemic myocardium.
  
  
  RESULTS
  Adenosine receptor blockade did not affect left ventricular function assessed from heart rate x pressure product and pressure x volume work although coronary flow was slightly reduced. Adenosine receptor blockade increased glucose uptake (P < 0.05) by 100% during preischaemia and by 74% during mild hypoperfusion, and increased lactate production from exogenous glucose (P < 0.05) by 89% during preischaemia and fourfold during mild hypoperfusion, but did not stimulate glucose oxidation under any condition. Glycogen degradation was not increased by adenosine receptor blockade during ischaemia. Crossover plots of glycolytic intermediates revealed that phosphofructokinase was activated by adenosine receptor blockade at all three levels of perfusion.
  
  
  CONCLUSIONS
  Endogenous adenosine attenuates anaerobic glycolysis in normally perfused, hypoperfused and ischaemic myocardium by blunting phosphofructokinase activity; this effect is mediated by adenosine A1 receptors.
authors.affiliation: Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth 76107-2699, USA.
authors.forename: Z P
authors.initials: ZP
authors.lastname: Gao
authors.forename: H F
authors.initials: HF
authors.lastname: Downey
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: M X
authors.initials: MX
authors.lastname: He
authors.forename: R T
authors.initials: RT
authors.lastname: Mallet
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010477:Perfusion; D010732:Phosphofructokinase-1 / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D016277:Ventricular Function, Left
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D019344:Lactic Acid; C031433:8-(4-sulfophenyl)theophylline; D006003:Glycogen; D013806:Theophylline; D010732:Phosphofructokinase-1; D005947:Glucose; D000241:Adenosine