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Cellular and molecular mechanism(s) of coronary flow regulation by adenosine

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Summary

There is strong evidence in favor of a major role for adenosine in the metabolic regulation of blood flow to the heart. The exact nature of the molecular and cellular events leading to the vasodilatation by adenosine are poorly understood. In the present report we have provided experimental evidence that; (i) hypoxia of cardiac cells resulted in the production of adenosine (and its degradative products) which can be responsible for the hypoxic dilation observed by several workers; (ii) the release of metabolites such as potassium and inorganic phosphate was unchanged due to a 30-minute hypoxia of cardiac cells; (iii) the release of prostaglandin E but not F was enhanced due to hypoxia of cardiac cells which may be due to the storage pools in the cells; (iv) prostaglandin E1, E2 and F inhibited the uptake of adenosine at pharmacological concentrations but not at physiological concentrations; (v) prostaglandin synthetase inhibitors (aspirin and indomethacin) nonspecifically inhibited the uptake of adenosine in the cardiac cells; (vi) lowering of pH resulted in inhibition in the uptake of adenosine and its incorporation into adenine nucleotides in cardiac cells; (vii) lowering the pH of the perfusion medium resulted in the increased release of perfusate adenosine (and its degradative products) with a simultaneous increase in coronary blood flow; (ix) specific adenosine receptor sites were found in cardiac muscle, coronary arteries, and carotid arteries of the dog and rabbit aorta, which satisfy the basic characteristic of receptor binding; and (x) these receptor binding sites were different from the adenosine uptake protein and were competitively blocked by theophylline or aminophylline. It is concluded that adenosine plays a major role in blood flow regulation to the heart and acts through specific receptors to produce vasodilatation.

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References

  1. 1.

    Drury, A. N. and Szent-Györgyi, A., 1929. J. Physiol. 68, 213–237.

  2. 2.

    Berne, R. M., 1963. Am. J. Physiol. 204, 317–322.

  3. 3.

    Baer, H. P. and Drummond, G. I., eds., 1979. In “Physiological and Regulatory Functions of Adenosine and Adenine Nucleotides”, Reven Press, New York.

  4. 4.

    Arch, J. R. S. and Newsholme, E. A., 1978. In “Essays in Biochemistry” (Campbell, P. N. and Aldridge, W. N., eds.) Vol. 14, pp. 82–123, Academic Press, New York.

  5. 5.

    Fox, I. H. and Kelly, W. N., 1978. Ann. Rev. Biochem 47, 655–686.

  6. 6.

    Olsson, R. A. and Patterson, R. E., 1976. Prog. Mol. Subcell. Biol 4, 227–248.

  7. 7.

    Berne, R. M. and Rubio, R., 1977. In “Brain and Heart Infarcts”, (Zulch, K. T., Kaufmann, W., Hossman, K. A. and Hossman, V., eds.) pp. 19–29, Springer-Verlag, Berlin.

  8. 8.

    Berne, R. M. and Rubio, R., 1978. In “Mechanisms of Vasodilatation”, (Vanhoutte, P. M. and Leusen, I., eds.) pp. 214–221, S. Krager, New York.

  9. 9.

    Rubio, R., Berne, R. M. and Dobson, J. G., Jr., 1973. Am. J. Physiol. 225, 938–953.

  10. 10.

    Rubio, R. and Berne, R. M., 1969. Circ. Res. 25, 407–415.

  11. 11.

    Rubio, R., Wiedmeier, V. T. and Berne, R. M., 1974. J. Mol. Cell. Cardiol. 6, 561–566.

  12. 12.

    Berne, R. M., Rubio, R. and Duling, B. R., 1971. In “Myocardial Ischemia”, Exerpta Medica, Amsterdam, pp. 28–43.

  13. 13.

    Berne, R. M., Rubio, R., Duling, B. R. and Wiedmeier, V. T., 1970. Adv. Cardiol. 5, 56–66.

  14. 14.

    Olsson, R. A., 1970. Circ. Res. 26, 301–306.

  15. 15.

    Fox, A. C., Reed, G. E., Glassman, E., Kaltman, A. J. and Silk, B. B., 1974. J. Clin. Invest 53, 1447–1457.

  16. 16.

    Foley, D. H., Herlihy, J. T., Thompson, C. I., Rubio, R. and Berne, R. M., 1978. J. Mol. Cell. Cardiol. 10, 292–300.

  17. 17.

    Watkinson, W. P., Foley, D. H., Rubio, R. and Berne, R. M., 1979. Am. J. Physiol. 236, H13-H21.

  18. 18.

    McKenzie, J. E., McCoy, F. P. and Bockman, E. L., 1979. Fed. Proc. 38, 1037, (Abstr.).

  19. 19.

    Berne, R. M. and Rubio, R., 1977. Adv. Exptl. Biol. Med. 78, 163–174.

  20. 20.

    Wiedmeier, V. T. and Spell, L. H., 1977. Circ. Res. 41, 503–508.

  21. 21.

    Sattin, A. and Rall, T. W., 1970. Mol. Pharmacol. 6, 13–23.

  22. 22.

    Triner, L., Nahas, G. G., Vuliemoz, Y., Overweg, N. I. A., Verosky, M., Habif, D. V. and Hgai, S. H., 1971, Ann. N.Y. Acad. Sci. 185, 458–476.

  23. 23.

    Herlihy, J. T., Bockman, E. L., Berne, R. M. and Rubio, R., 1976. Am. J. Physiol. 230, 1239–1243.

  24. 24.

    Verhaeghe, R. H., 1977. Am. J. Physiol. 233, H114-H121.

  25. 25.

    McKenzie, S. G., Frew, R. and Baer, H. P., 1977. Eur. J. Pharmacol. 41, 183–192.

  26. 26.

    Kukovetz, W. R., 1979. In “Physiological and Regulatory Functions of Adenosine and Adenine Nucleotides”, (Baer, H. P. and Drummond, G. I., eds.) pp. 205–213, Raven Press, New York.

  27. 27.

    Schrader, J., Rubio, R. and Berne, R. M., 1975. J. Mol. Cell. Cardiol. 7, 427–433.

  28. 28.

    Afonso, S., 1970. Circ. Res. 26, 743–752.

  29. 29.

    Scholtholt, J., Nitz, R. E. and Schraven, E., 1972. Arzneim Forsch 22, 1255–1259.

  30. 30.

    Cobbin, L. B., Einstein, R. and Maguire, M. H., 1974. Brit. J. Pharmacol. 50, 23–33.

  31. 31.

    Burnstock, G., 1979. In “Physiological and Regulatory Functions of Adenosine and Adenine Nucleotides”, (Baer, H. P. and Drummond, G. L, eds.) pp. 3–32, Raven Press, New York.

  32. 32.

    Plagemann, P. G. W. and Richey, D. P., 1974. Biochim. Biophys. Acta 344, 263–305.

  33. 33.

    Paalzow, L. W., 1975. J. Phrmacokinet. Biopharmacol. 3, 25–38.

  34. 34.

    Olsson, R. A., Davis, C. J., Khouri, E. M. and Patterson, R. E., 1976. Circ. Res. 39, 93–98.

  35. 35.

    Olsson, R. A., Davis, C. J. and Khouri, E. M., 1977. Life Sci. 21, 1343–1350.

  36. 36.

    Bunger, R., Haddy, F. J. and Gerlach, E., 1975. Pflugers Arch. 358, 213–224.

  37. 37.

    Stein, H. H., Somani, P. and Parsad, R. N., 1975. Ann. N.Y. Acad. Sci. 255, 380–389.

  38. 38.

    Schrader, J., Nees, S. and Gerlach, E., 1977. Pflugers Arch. 369, 251–257.

  39. 39.

    Northover, B. J., 1972. Brit. J. Phrmacol. 45, 651–659.

  40. 40.

    Murray, P. A. and Sparks, H. V., 1978. Circ. Res. 42, 35–42.

  41. 41.

    Parratt, J. R. and Marshall, R. J., 1978. Acta Biol. Med. Germ. 37, 747–760.

  42. 42.

    Blass, K. E., Zehl, U. and Forster, W., 1976. Acta Biol. Med. Germ. 35, 1161–1162.

  43. 43.

    Logan, M. E. and Wiedmeier, V. T., 1973. Fed. Proc. 32, 787 (Abstr.).

  44. 44.

    Merrill, G. F., Haddy, F. J. and Dabney, J. M., 1978. Circ. Res. 42, 225–229.

  45. 45.

    DeJong, J. W. and Kalkman, C., 1973. Biochim. Biophys. Acta 320, 388–396.

  46. 46.

    Gellai, M., Norton, J. M. and Detar, R., 1973. Circ. Res. 32, 279–289.

  47. 47.

    Moir, T. W. and Jones, P. K., 1973. Adv. Exptl. Biol. Med. 39, 11–26.

  48. 48.

    Raberger, B., Schultz, W. and Kraupp, O., 1975. Clin. Exptl. Pharmacol. Physiol. 2, 373–382.

  49. 49.

    Echenhoff, J. E., Hafkenshiel, J. H. and Landmesser, C. M., 1947. Am. J. Physiol. 148, 582–596.

  50. 50.

    Scott, J. B. and Radawski, D., 1971. Cite. Res. 28 (Suppl. 1), 26–32.

  51. 51.

    Schrader, J., Baummann, G. and Gerlach, E., 1977. Pflugers Arch. 372, 29–35.

  52. 52.

    Schultz, J. and Daly, J. W., 1973. J. Biol. Chem. 248, 853–859.

  53. 53.

    Haslam, R. J. and Rosson, G. M., 1975. Mol. Pharmacol. 11, 528–544.

  54. 54.

    Malbon, C. C., Hert, R. and Fain, J. N., 1978. J. Biol. Chem. 253, 3114–3122.

  55. 55.

    Peck, W. A., Carpenter, J. and Messinger, K., 1974. 91, 148–154.

  56. 56.

    Dutta, P. and Mustafa, S. J., 1979. J. Pharmacol. Exptl. Therap. 211, 496–501.

  57. 57.

    Dutta, P. and Mustafa, S. J., (in press). J. Pharmacol. Exptl. Therap.

  58. 58.

    Ghai, G., and Mustafa, S. J., (in press). J. Pharmacol. Exptl. Therap.

  59. 59.

    VanHarn, G. L., Rubio, R. and Berne, R. M., 1977. Am. J. Physiol. 233, H299-H304.

  60. 60.

    Mustafa, S. J., Berne, R. M. and Rubio, R., 1975. Am. J. Physiol. 288, 1474–1478.

  61. 61.

    Mustafa, S. J., (in press). J. Mol. Cell. Cardiol.

  62. 62.

    Gentry, M. K. and Olsson, R. A., 1975. Anal. Biochem. 64, 624–627.

  63. 63.

    Wiedmier, V. T., Morris, R. and Logan, M. E., 1978. Fed. Proc. 37, 565.

  64. 64.

    Harder, D. R., Belardinelli, L., Sperelakis, N., Rubio, R. and Berne, R. M., 1979. Circ. Res. 44, 176–182.

  65. 65.

    Schanar, R. L. and Sparks, H. V., 1972, Am. J. Physiol. 223, 223–228.

  66. 66.

    Pearson, J. D., Carleton, J. S., Hutchings, A. and Gordon, J. L., 1978. Biochem. J. 170, 265–271.

  67. 67.

    Olsson, R. A., Vomacka, R. B. and Nixon, D. G., 1979. In “Physiological and Regulatory Functions of Adenosine and Adenine Nucleotides”, (Baer, H. P. and Drummond, G. L, eds.) pp. 297–304, Raven Press, New York.

  68. 68.

    Yuh, K. M. and Tao, M., 1974. Biochemistry 13, 5220–5226.

  69. 69.

    Sugden, P. H. and Corbin, J. D., 1976. Biochem. J. 159, 423–437.

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Mustafa, S.J. Cellular and molecular mechanism(s) of coronary flow regulation by adenosine. Mol Cell Biochem 31, 67–87 (1980). https://doi.org/10.1007/BF00240813

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Key Words

  • Adenosine Receptor
  • Coronary Circulation
  • Vasoactive Metabolites