Role of Capillary Endothelial Cells in Transport and Metabolism of Adenosine in the Heart: An Example of the Impact of Endothelial Cells on Measures of Metabolism

  • Keith Kroll
  • James Bassingthwaighte


Endothelial cells, lying between the blood stream and the parenchymal cells of an organ, are a part of the set of signaling paths for the organ. Sensing blood solute concentrations or sensing intravascular shear can lead to the endothelial production of substances sensed or taken up by other cells. The interactions between endothelium and smooth muscle fall into a special class relating to the regulation of vasomotion. A component of the vasoregulatory system concerns the regulation of interstitial adenosine; understanding of adenosine in endothelial cells and myocytes has come slowly from early beginnings (Berne et al., 1983) and from studies of transport and exchange (Bassingthwaighte et al., 1985a,b; Gorman et al., 1986). In this chapter we provide a further set of ideas on relationships between endothelial cells and cardiac myocytes in vivo, using adenosine as the substrate of interest. These ideas hold for a variety of solutes, substrates, agonists, and pharmacologic agents, which one can choose to contemplate while reading about this local adenosine story.


Adenosine Deaminase Capillary Endothelial Cell Adenosine Kinase Adenosine Concentration Adenosine Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arch, J. R. S. and E. A. Newsholme. Activities and some properties of 5′-nucleotidase adenosine kinase and adenosine deaminase in tissues from vertebrates and invertebrates in relation to the control of the concentration and the physiological role of adenosine. Biochem. J. 174:965–977, 1978.PubMedGoogle Scholar
  2. Bardenheuer, H. and J. Schrader. Supply-to-demand ratio for oxygen determines formation of adenosine by the heart. Am. J. Physiol. 250 (Heart Circ. Physiol. 19):H173–H180, 1986.PubMedGoogle Scholar
  3. Bassingthwaighte, J. B., H. V. Sparks, Jr., I. S. Chan, D. F. DeWitt, and M. W. Gorman. Modeling of transendothelial transport. Fed. Proc. 44:2623–2626, 1985a.PubMedGoogle Scholar
  4. Bassingthwaighte, J. B., C. Y. Wang, M. Gorman, D. DeWitt, I. S. Chan, and H. V. Sparks. Endothelial regulation of agonist and metabolite concentrations in the interstitium. In: Carrier-Mediated Transport of Solutes from Blood to Tissue, edited by D. L. Yudilevich and G. E. Mann. New York: Longman, pp. 191–203, 1985b.Google Scholar
  5. Bassingthwaighte, J. B., C. Y. Wang, and I. S. Chan. Blood-tissue exchange via transport and transformation by endothelial cells. Circ. Res. 65:997–1020, 1989.PubMedGoogle Scholar
  6. Berne, R. M., R. M. Knabb, S. W. Ely, and R. Rubio. Adenosine in the local regulation of blood flow: A brief overview. Fed. Proc. 42:3136–3142, 1983.PubMedGoogle Scholar
  7. Bontemps, F., G. Van den Berghe, and H. G. Hers. Evidence for a substrate cycle between AMP and adenosine in isolated hepatocytes. Proc. Natl. Acad. Sci. USA 80:2829–2833, 1983.PubMedCrossRefGoogle Scholar
  8. Catravas, J. D. Removal of adenosine from the rabbit pulmonary circulation, in vivo and in vitro. Circ. Res. 54:603–611, 1984.PubMedGoogle Scholar
  9. Clemo, H. F. and L. Belardinelli. Effect of adenosine on atrioventricular conduction. I: Site and characterization of adenosine action in the guinea pig atrioventricular node. Circ. Res. 59(4):427–436, 1986.PubMedGoogle Scholar
  10. Deussen, A., M. Borst, K. Kroll, and J. Schrader. Formation of S-adenosylhomocysteine in the heart. II. A sensitive index for regional myocardial underperfusion. Circ. Res. 63:250–261, 1988.PubMedGoogle Scholar
  11. Deussen, A., H. G. E. Lloyd, and J. Schrader. Contribution of S-adenosylhomocysteine to cardiac adenosine formation. J. Mol. Cell Cardiol. 21:773–782, 1989.PubMedCrossRefGoogle Scholar
  12. Ford, D. A. and M. J. Rovetto. Rat cardiac myocyte adenosine transport and metabolism. Am. J. Physiol. 252 (1 Pt. 2):H54–H63, 1987.PubMedGoogle Scholar
  13. Gorman, M. W., J. B. Bassingthwaighte, R. A. Olsson, and H. V. Sparks. Endothelial cell uptake of adenosine in canine skeletal muscle. Am. J. Physiol. 250 (Heart Circ. Physiol. 19):H482–H489, 1986.PubMedGoogle Scholar
  14. Kang, Y. H., R. T. Mallet, and R. Bunger. Coronary autoregulation and purine release in normoxic heart at various cytoplasmic phosphorylation potentials: Disparate effects of adenosine. Eur. J. Physiol. 421:188–199, 1992.CrossRefGoogle Scholar
  15. Kroll, K. and J. B. Bassingthwaighte. Capillary endothelial cell adenosine transport in guinea pig heart. Microcirculation 2:87, 1995.Google Scholar
  16. Kroll, K. and D. W. Stepp. Adenosine kinetics in the canine coronary circulation. Am. J. Physiol. 270 (Heart Circ. Physiol. 39):H1469–H1483, 1996.PubMedGoogle Scholar
  17. Kroll, K., J. Schrader, and D. Möllmann. Endothelial activation by adenosine and coronary flow regulation in the guinea pig heart. In: Topics and Perspectives in Adenosine Research, edited by E. Gerlach and B. F. Becker. Berlin/Heidelberg: Springer-Verlag, pp. 470–479, 1987.Google Scholar
  18. Kroll, K., A. Deussen, and I. R. Sweet. Comprehensive model of transport and metabolism of adenosine and S-adenosylhomocysteine in the guinea pig heart. Circ. Res. 71:590–604. 1992.PubMedGoogle Scholar
  19. Kroll, K., U. Decking, K. Dreikorn, and J. Schrader. Rapid turnover of the AMP-adenosine metabolic cycle in the guinea pig heart. Circ. Res. 73:846–856, 1993.PubMedGoogle Scholar
  20. Kroll, K., D. J. Kinzie, and L. A. Gustafson. Open system kinetics of myocardial phos-phoenergetics during coronary underperfusion. Am. J. Physiol. 272:H2563–H2576, 1997.PubMedGoogle Scholar
  21. Kuikka, J., M. Levin, and J. B. Bassingthwaighte. Multiple tracer dilution estimates of D-and 2-deoxy-D-glucose uptake by the heart. Am. J. Physiol. 250 (Heart Circ. Physiol. 19):H29–H42, 1986.PubMedGoogle Scholar
  22. Nees, S., V. Herzog, B. F. Becker, M. Böck, C. Des Rosiers, and E. Gerlach. The coronary endothelium: A highly active metabolic barrier for adenosine. Basic Res. Cardiol. 80:515–529, 1985.PubMedCrossRefGoogle Scholar
  23. Pearson, J. D., J. S. Carleton, A. Hutchings, and J. L. Gordon. Uptake and metabolism of adenosine by pig aortic endothelial and smooth-muscle cells in culture. Biochem. J. 170:265–271, 1978.PubMedGoogle Scholar
  24. Plagemann, P. G. W. and R. M. Wohlhueter. Effects of nucleoside transport inhibitors on the salvage and toxicity of adenosine and deoxyadenosine in L1210 and P338 mouse leukemia cells. Cancer Res. 45:6418–6424, 1985.PubMedGoogle Scholar
  25. Plagemann, P. G. W., R. M. Wohlhueter, and M. Kraupp. Adenosine uptake, transport, and metabolism in human erythrocytes. J. Cell. Physiol. 125:330–336, 1985.PubMedCrossRefGoogle Scholar
  26. Saito, D., C. R. Steinhart, D. G. Nixon, and R. A. Olsson. Intracoronary adenosine deaminase reduces canine myocardial reactive hyperemia. Circ. Res. 49:1262–1267, 1981.PubMedGoogle Scholar
  27. Schrader, J. and E. Gerlach. Compartmentation in cardiac adenine nucleotides and formation of adenosine. Pflügers Arch. 367:129–135, 1976.PubMedCrossRefGoogle Scholar
  28. Schrader, J., G. Baumann, and E. Gerlach. Adenosine as inhibitor of myocardial effects of catecholamines. Eur. J. Physiol. 372:29–35, 1977.CrossRefGoogle Scholar
  29. Schwartz, L. M., T. R. Bukowski, J. H. Revkin, and J. B. Bassingthwaighte. Species differences in capillary transport of inosine and adenosine in rabbit and guinea pig hearts. FASEB J. 2:A1524, 1988.Google Scholar
  30. Schwartz, L. M., T. R. Bukowski, and J. B. Bassingthwaighte. Indicator dilution estimates of adenosine transport kinetics in cardiac capillary endothelial cells of guinea pigs. FASEB J. 3:A269, 1989.Google Scholar
  31. Schwartz, L. M., T. R. Bukowski, and J. B. Bassingthwaighte. Indicator dilution estimates of adenosine capillary transport kinetics in guinea pig hearts. Am. J. Physiol. 270 (Heart Circ. Physiol. 39), in review.Google Scholar
  32. Stepp, D. W., R. van Bibber, K. Kroll, and E. O. Feigl. Quantitative relation between interstitial adenosine concentration and coronary blood flow. Circ. Res. 79:601–610, 1996.PubMedGoogle Scholar
  33. Stirling, C. E. Autoradiographic localization of 3H-adenosine. In: Regulatory Function of Adenosine, edited by R. M. Berne, T. W. Rail, and R. Rubio. Boston: Martinus Nijhoff, 1983, p. 542.Google Scholar
  34. Wangler, R. D., M. W. Gorman, C. Y. Wang, D. F. DeWitt, I. S. Chan, J. B. Bassingthwaighte, and H. V. Sparks. Transcapillary adenosine transport and interstitial adenosine concentration in guinea pig hearts. Am. J. Physiol. 257 (Heart Circ. Physiol. 26):H89–H106, 1989.PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1998

Authors and Affiliations

  • Keith Kroll
  • James Bassingthwaighte

There are no affiliations available

Personalised recommendations