The effects of the exogenous provision of lactate and the endogenous production of lactate on protein synthesis in the heart.
We have investigated the effects of exogenous addition of lactate and of the stimulation of endogenous production of lactate on protein synthesis in the anterogradely perfused rat heart. In the absence of exogenous lactate, hearts release lactate into the perfusate. At lactate concentrations of 0.2 mM and greater, the heart takes up lactate. The best fit for lactate uptake plotted against exogenous lactate concentration is a rectangular hyperbola with a maximal rate of 220 mumol/2 h per heart (wet wt. about 1 g). Uptake is half-maximal at about 1.3 mM-lactate. The stimulation of protein synthesis also exhibits a rectangular-hyperbolic dependence on exogenous lactate concentration, with maximal stimulation being about 38%. Half-maximal stimulation occurs at about 0.9 mM-lactate. We stimulated endogenous lactate production by perfusion with 2-cyanocinnamate (an inhibitor of mitochondrial pyruvate transport) at concentrations up to 70 microM. Cardiac outputs, intracellular pH and the concentrations of phosphocreatine and the adenine nucleotides were not altered. Atrial protein-synthesis rates were unchanged, but ventricular rates were decreased. We conclude that endogenous lactate production is unlikely to stimulate protein synthesis and that the stimulation of protein synthesis by exogenous lactate is related to its uptake.
Fuller
S J
SJ
Department of Cardiac Medicine, National Heart and Lung Institute (University of London), U.K.
Sugden
P H
PH
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002934:Cinnamates / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D014176:Protein Biosynthesis; D011773:Pyruvates / Q000378:metabolism; D051381:Rats
D000227:Adenine Nucleotides; D002934:Cinnamates; D007328:Insulin; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D011773:Pyruvates; D010725:Phosphocreatine; C018253:alpha-cyanocinnamate; D005947:Glucose; D007545:Isoproterenol; D004837:Epinephrine