(Circulation. 1999;99:2041-2047.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Quantification of Extracellular and Intracellular Adenosine Production
Understanding the Transmembranous Concentration Gradient
From the Institut für Physiologie, Medizinische Fakultät Carl Gustav Carus, TU Dresden (A.D., M.S.), and the Klinik für Kardiologie, Pneumologie, und Angiologie, Heinrich-Heine-Universität Düsseldorf (S.S., M.K.), Germany.
Correspondence to Dr Andreas Deussen, Professor and Chairman, Institut für Physiologie, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Fetscherstraße 74, D-01307 Dresden, Germany.
Background—Inhibitors of adenosine membrane transport cause vasodilation and enhance the plasma adenosine concentration. However, it is unclear why the plasma adenosine concentration rises rather than falls when membrane transport is inhibited. We tested the hypothesis that the cytosolic adenosine concentration exceeds the interstitial concentration under well-oxygenated conditions.
Methods and Results—In isolated, isovolumically working guinea
pig hearts (n=50), the release rate of adenosine and
accumulation of S-adenosylhomocysteine (after 20 minutes
of 200 µmol/L homocysteine), a measure of the free cytosolic
adenosine concentration, were determined in the absence and
presence of specific and powerful blockers of adenosine
membrane transport (nitrobenzylthioinosine 1 µmol/L),
adenosine deaminase (erythro-9-hydroxy-nonyl-adenine 5
µmol/L), and adenosine kinase (iodotubericidine 10
µmol/L). Data analysis with a distributed multicompartment
model revealed a total cardiac adenosine production
rate of 2294 pmol · min-1 ·
g-1, of which 8% was produced in the extracellular
region. Because of a high rate of intracellular metabolism,
however, 70.3% of extracellularly produced adenosine was taken
up into cellular regions, an effect that was effectively eliminated by
membrane transport block. The resulting 
2.8-fold increase of the
interstitial adenosine concentration evoked
near-maximal coronary dilation.
Conclusions—We rejected the hypothesis that the cytosolic adenosine concentration exceeds the interstitial. Rather, there is significant extracellular production, and the parenchymal cell represents a sink, not a source, for adenosine under well-oxygenated conditions.
Key Words: adenosine • blood flow • inosine • S-adenosylhomocysteine
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