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. 1988 Feb 1;249(3):695–703. doi: 10.1042/bj2490695

Absolute rates of adenosine formation during ischaemia in rat and pigeon hearts.

P Meghji 1, K M Middleton 1, A C Newby 1
PMCID: PMC1148762  PMID: 2833226

Abstract

1. The activities of ecto- and cytosolic 5'-nucleotidase (EC 3.1.3.5), adenosine kinase (EC 2.7.1.20), adenosine deaminase (EC 3.5.4.4) and AMP deaminase (EC 3.5.4.6) were compared in ventricular myocardium from man, rats, rabbits, guinea pigs, pigeons and turtles. The most striking variation was in the activity of the ecto-5'-nucleotidase, which was 20 times less active in rabbit heart and 300 times less active in pigeon heart than in rat heart. The cytochemical distribution of ecto-5'-nucleotidase was also highly variable between species. 2. Adenosine formation was quantified in pigeon and rat ventricular myocardium in the presence of inhibitors of adenosine kinase and adenosine deaminase. 3. Both adenosine formation rates and the proportion of ATP catabolized to adenosine were greatest during the first 2 min of total ischaemia at 37 degrees C. Adenosine formation rates were 410 +/- 40 nmol/min per g wet wt. in pigeon hearts and 470 +/- 60 nmol/min per g wet wt. in rat hearts. Formation of adenosine accounted for 46% of ATP plus ADP broken down in pigeon hearts and 88% in rat hearts. 4. The data show that, in both pigeon and rat hearts, adenosine is the major catabolite of ATP in the early stages of normothermic myocardial ischaemia. The activity of ecto-5'-nucleotidase in pigeon ventricle (16 +/- 4 nmol/min per g wet wt.) was insufficient to account for adenosine formation, indicating the existence of an alternative catabolic pathway.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Achterberg P. W., Harmsen E., de Jong J. W. Adenosine deaminase inhibition and myocardial purine release during normoxia and ischaemia. Cardiovasc Res. 1985 Oct;19(10):593–598. doi: 10.1093/cvr/19.10.593. [DOI] [PubMed] [Google Scholar]
  2. Agarwal R. P., Spector T., Parks R. E., Jr Tight-binding inhibitors--IV. Inhibition of adenosine deaminases by various inhibitors. Biochem Pharmacol. 1977 Mar 1;26(5):359–367. doi: 10.1016/0006-2952(77)90192-7. [DOI] [PubMed] [Google Scholar]
  3. Arch J. R., Newsholme E. A. 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. 1978 Sep 15;174(3):965–977. doi: 10.1042/bj1740965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Avruch J., Wallach D. F. Preparation and properties of plasma membrane and endoplasmic reticulum fragments from isolated rat fat cells. Biochim Biophys Acta. 1971 Apr 13;233(2):334–347. doi: 10.1016/0005-2736(71)90331-2. [DOI] [PubMed] [Google Scholar]
  5. Belardinelli L., Belloni F. L., Rubio R., Berne R. M. Atrioventricular conduction disturbances during hypoxia. Possible role of adenosine in rabbit and guinea pig heart. Circ Res. 1980 Nov;47(5):684–691. doi: 10.1161/01.res.47.5.684. [DOI] [PubMed] [Google Scholar]
  6. Belardinelli L., Mattos E. C., Berne R. M. Evidence for adenosine mediation of atrioventricular block in the ischemic canine myocardium. J Clin Invest. 1981 Jul;68(1):195–205. doi: 10.1172/JCI110235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Berne R. M. The role of adenosine in the regulation of coronary blood flow. Circ Res. 1980 Dec;47(6):807–813. doi: 10.1161/01.res.47.6.807. [DOI] [PubMed] [Google Scholar]
  8. Burger R. M., Lowenstein J. M. 5'-Nucleotidase from smooth muscle of small intestine and from brain. Inhibition of nucleotides. Biochemistry. 1975 Jun 3;14(11):2362–2366. doi: 10.1021/bi00682a014. [DOI] [PubMed] [Google Scholar]
  9. CHANEY A. L., MARBACH E. P. Modified reagents for determination of urea and ammonia. Clin Chem. 1962 Apr;8:130–132. [PubMed] [Google Scholar]
  10. DeBoer L. W., Ingwall J. S., Kloner R. A., Braunwald E. Prolonged derangements of canine myocardial purine metabolism after a brief coronary artery occlusion not associated with anatomic evidence of necrosis. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5471–5475. doi: 10.1073/pnas.77.9.5471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Degenring F. H., Rubio R., Berne R. M. Adenine nucleotide metabolism during cardiac hypertrophy and ischemia in rats. J Mol Cell Cardiol. 1975 Feb;7(2):105–113. doi: 10.1016/0022-2828(75)90012-7. [DOI] [PubMed] [Google Scholar]
  12. Deuticke B., Gerlach E., Dierkesmann R. Abbau freier Nucleotide in Herz, Skeletmuskel, Gehirn und Leber der Ratte bei Sauerstoffmangel. Pflugers Arch Gesamte Physiol Menschen Tiere. 1966;292(3):239–254. [PubMed] [Google Scholar]
  13. Dobson J. G., Jr Mechanism of adenosine inhibition of catecholamine-induced responses in heart. Circ Res. 1983 Feb;52(2):151–160. doi: 10.1161/01.res.52.2.151. [DOI] [PubMed] [Google Scholar]
  14. Dobson J. G., Jr Reduction by adenosine of the isoproterenol-induced increase in cyclic adenosine 3',5'-monophosphate formation and glycogen phosphorylase activity in rat heart muscle. Circ Res. 1978 Nov;43(5):785–792. doi: 10.1161/01.res.43.5.785. [DOI] [PubMed] [Google Scholar]
  15. Drury A. N., Szent-Györgyi A. The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J Physiol. 1929 Nov 25;68(3):213–237. doi: 10.1113/jphysiol.1929.sp002608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Edlund A., Fredholm B. B., Patrignani P., Patrono C., Wennmalm A., Wennmalm M. Release of two vasodilators, adenosine and prostacyclin, from isolated rabbit hearts during controlled hypoxia. J Physiol. 1983 Jul;340:487–501. doi: 10.1113/jphysiol.1983.sp014775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Endoh M., Yamashita S. Adenosine antagonizes the positive inotropic action mediated via beta-, but not alpha-adrenoceptors in the rabbit papillary muscle. Eur J Pharmacol. 1980 Aug 8;65(4):445–448. doi: 10.1016/0014-2999(80)90352-0. [DOI] [PubMed] [Google Scholar]
  18. Fisher M. N., Newsholme E. A. Properties of rat heart adenosine kinase. Biochem J. 1984 Jul 15;221(2):521–528. doi: 10.1042/bj2210521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Foley D. H., Herlihy J. T., Thompson C. I., Rubio R., Berne R. M. Increased adenosine formation by rat myocardium with acute aortic constriction. J Mol Cell Cardiol. 1978 Mar;10(3):293–300. doi: 10.1016/0022-2828(78)90352-8. [DOI] [PubMed] [Google Scholar]
  20. Frick G. P., Lowenstein J. M. Studies of 5'-nucleotidase in the perfused rat heart. Including measurements of the enzyme in perfused skeletal muscle and liver. J Biol Chem. 1976 Oct 25;251(20):6372–6378. [PubMed] [Google Scholar]
  21. Fritzson P., Haugen T. B., Tjernshaugen H. The presence and activity in normal and regenerating rat liver postmicrosomal supernatant fraction of an enzyme with properties similar to those of membrane-bound 5'-nucleotidase. Biochem J. 1986 Oct 1;239(1):185–190. doi: 10.1042/bj2390185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hedqvist P., Fredholm B. B. Inhibitory effect of adenosine on adrenergic neuroeffector transmission in the rabbit heart. Acta Physiol Scand. 1979 Jan;105(1):120–122. doi: 10.1111/j.1748-1716.1979.tb06321.x. [DOI] [PubMed] [Google Scholar]
  23. IMAI S., RILEY A. L., BERNE R. M. EFFECT OF ISCHEMIA ON ADENINE NUCLEOTIDES IN CARDIAC AND SKELETAL MUSCLE. Circ Res. 1964 Nov;15:443–450. doi: 10.1161/01.res.15.5.443. [DOI] [PubMed] [Google Scholar]
  24. Itoh R., Oka J. Evidence for existence of a cytosol 5'-nucleotidase in chicken heart: comparison of some properties of heart and liver enzymes. Comp Biochem Physiol B. 1985;81(1):159–163. doi: 10.1016/0305-0491(85)90177-4. [DOI] [PubMed] [Google Scholar]
  25. Itoh R., Oka J., Ozasa H. Regulation of rat heart cytosol 5'-nucleotidase by adenylate energy charge. Biochem J. 1986 May 1;235(3):847–851. doi: 10.1042/bj2350847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. James T. N. The chronotropic action of ATP and related compounds studied by direct perfusion of the sinus node. J Pharmacol Exp Ther. 1965 Aug;149(2):233–247. [PubMed] [Google Scholar]
  27. KARLSSON U., SCHULTZ R. L. FIXATION OF THE CENTRAL NERVOUS SYSTEM FROM ELECTRON MICROSCOPY BY ALDEHYDE PERFUSION. I. PRESERVATION WITH ALDEHYDE PERFUSATES VERSUS DIRECT PERFUSION WITH OSMIUM TETROXIDE WITH SPECIAL REFERENCE TO MEMBRANES AND THE EXTRACELLULAR SPACE. J Ultrastruct Res. 1965 Feb;12:160–186. doi: 10.1016/s0022-5320(65)80014-4. [DOI] [PubMed] [Google Scholar]
  28. Lee K. S., Schubert P., Reddington M., Kreutzberg G. W. The distribution of adenosine A1 receptors and 5'-nucleotidase in the hippocampal formation of several mammalian species. J Comp Neurol. 1986 Apr 22;246(4):427–434. doi: 10.1002/cne.902460402. [DOI] [PubMed] [Google Scholar]
  29. Lokhandwala M. F. Inhibition of cardiac sympathetic neurotransmission by adenosine. Eur J Pharmacol. 1979 Dec 20;60(4):353–357. doi: 10.1016/0014-2999(79)90241-3. [DOI] [PubMed] [Google Scholar]
  30. Lomax C. A., Henderson J. F. Adenosine formation and metabolism during adenosine triphosphate catabolism in Ehrlich ascites tumor cells. Cancer Res. 1973 Nov;33(11):2825–2829. [PubMed] [Google Scholar]
  31. Low M. G. Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors. Biochem J. 1987 May 15;244(1):1–13. doi: 10.1042/bj2440001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mauser M., Hoffmeister H. M., Nienaber C., Schaper W. Influence of ribose, adenosine, and "AICAR" on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog. Circ Res. 1985 Feb;56(2):220–230. doi: 10.1161/01.res.56.2.220. [DOI] [PubMed] [Google Scholar]
  33. Meghji P., Holmquist C. A., Newby A. C. Adenosine formation and release from neonatal-rat heart cells in culture. Biochem J. 1985 Aug 1;229(3):799–805. doi: 10.1042/bj2290799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Moss K. M. The effect of purine nucleotides and phosphate on the activity of AMP deaminase in a cytosol extract of rat liver. FEBS Lett. 1977 Mar 15;75(1):141–144. doi: 10.1016/0014-5793(77)80071-9. [DOI] [PubMed] [Google Scholar]
  35. Nakatsu K., Drummond G. I. Adenylate metabolism and adenosine formation in the heart. Am J Physiol. 1972 Nov;223(5):1119–1127. doi: 10.1152/ajplegacy.1972.223.5.1119. [DOI] [PubMed] [Google Scholar]
  36. Newby A. C., Holmquist C. A. Adenosine production inside rat polymorphonuclear leucocytes. Biochem J. 1981 Nov 15;200(2):399–403. doi: 10.1042/bj2000399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Newby A. C., Holmquist C. A., Illingworth J., Pearson J. D. The control of adenosine concentration in polymorphonuclear leucocytes, cultured heart cells and isolated perfused heart from the rat. Biochem J. 1983 Aug 15;214(2):317–323. doi: 10.1042/bj2140317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Newby A. C., Luzio J. P., Hales C. N. The properties and extracellular location of 5'-nucleotidase of the rat fat-cell plasma membrane. Biochem J. 1975 Mar;146(3):625–633. doi: 10.1042/bj1460625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Newby A. C. The interaction of inhibitors with adenosine metabolising enzymes in intact isolated cells. Biochem Pharmacol. 1981 Sep 15;30(18):2611–2615. doi: 10.1016/0006-2952(81)90589-x. [DOI] [PubMed] [Google Scholar]
  40. RICHMAN H. G., WYBORNY L. ADENINE NUCLEOTIDE DEGRADATION IN THE RABBIT HEART. Am J Physiol. 1964 Nov;207:1139–1145. doi: 10.1152/ajplegacy.1964.207.5.1139. [DOI] [PubMed] [Google Scholar]
  41. Reimer K. A., Hill M. L., Jennings R. B. Prolonged depletion of ATP and of the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs. J Mol Cell Cardiol. 1981 Feb;13(2):229–239. doi: 10.1016/0022-2828(81)90219-4. [DOI] [PubMed] [Google Scholar]
  42. Rubio R., Berne R. M., Dobson J. G., Jr Sites of adenosine production in cardiac and skeletal muscle. Am J Physiol. 1973 Oct;225(4):938–953. doi: 10.1152/ajplegacy.1973.225.4.938. [DOI] [PubMed] [Google Scholar]
  43. Schrader J., Baumann G., Gerlach E. Adenosine as inhibitor of myocardial effects of catecholamines. Pflugers Arch. 1977 Nov 25;372(1):29–35. doi: 10.1007/BF00582203. [DOI] [PubMed] [Google Scholar]
  44. Schrader J., Gerlach E. Compartmentation of cardiac adenine nucleotides and formation of adenosine. Pflugers Arch. 1976 Dec 28;367(2):129–135. doi: 10.1007/BF00585148. [DOI] [PubMed] [Google Scholar]
  45. Schrader J., Schütz W., Bardenheuer H. Role of S-adenosylhomocysteine hydrolase in adenosine metabolism in mammalian heart. Biochem J. 1981 Apr 15;196(1):65–70. doi: 10.1042/bj1960065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Schütz W., Schrader J., Gerlach E. Different sites of adenosine formation in the heart. Am J Physiol. 1981 Jun;240(6):H963–H970. doi: 10.1152/ajpheart.1981.240.6.H963. [DOI] [PubMed] [Google Scholar]
  47. Stanley K. K., Edwards M. R., Luzio J. P. Subcellular distribution and movement of 5'-nucleotidase in rat cells. Biochem J. 1980 Jan 15;186(1):59–69. doi: 10.1042/bj1860059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Swain J. L., Hines J. J., Sabina R. L., Holmes E. W. Accelerated repletion of ATP and GTP pools in postischemic canine myocardium using a precursor of purine de novo synthesis. Circ Res. 1982 Jul;51(1):102–105. doi: 10.1161/01.res.51.1.102. [DOI] [PubMed] [Google Scholar]
  49. Swain J. L., Sabina R. L., McHale P. A., Greenfield J. C., Jr, Holmes E. W. Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog. Am J Physiol. 1982 May;242(5):H818–H826. doi: 10.1152/ajpheart.1982.242.5.H818. [DOI] [PubMed] [Google Scholar]
  50. Thompson C. I., Rubio R., Berne R. M. Changes in adenosine and glycogen phosphorylase activity during the cardiac cycle. Am J Physiol. 1980 Mar;238(3):H389–H398. doi: 10.1152/ajpheart.1980.238.3.H389. [DOI] [PubMed] [Google Scholar]
  51. WACHSTEIN M., MEISEL E. Histochemistry of hepatic phosphatases of a physiologic pH; with special reference to the demonstration of bile canaliculi. Am J Clin Pathol. 1957 Jan;27(1):13–23. doi: 10.1093/ajcp/27.1.13. [DOI] [PubMed] [Google Scholar]
  52. WAHLER B. E., WOLLENBERGER A. Zur Bestimmung des Orthophosphats neben säure-molybdat-labilen Phosphorsäureverbindungen. Biochem Z. 1958;329(6):508–520. [PubMed] [Google Scholar]
  53. Ward H. B., St Cyr J. A., Cogordan J. A., Alyono D., Bianco R. W., Kriett J. M., Foker J. E. Recovery of adenine nucleotide levels after global myocardial ischemia in dogs. Surgery. 1984 Aug;96(2):248–255. [PubMed] [Google Scholar]
  54. Worku Y., Newby A. C. Nucleoside exchange catalysed by the cytoplasmic 5'-nucleotidase. Biochem J. 1982 Sep 1;205(3):503–510. doi: 10.1042/bj2050503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Worku Y., Newby A. C. The mechanism of adenosine production in rat polymorphonuclear leucocytes. Biochem J. 1983 Aug 15;214(2):325–330. doi: 10.1042/bj2140325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wotring L. L., Townsend L. B. Study of the cytotoxicity and metabolism of 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine using inhibitors of adenosine kinase and adenosine deaminase. Cancer Res. 1979 Aug;39(8):3018–3023. [PubMed] [Google Scholar]
  57. de Jong J. W., Kalkman C. Myocardial adenosine kinase: activity and localization determined with rapid, radiometric assay. Biochim Biophys Acta. 1973 Sep 14;320(2):388–396. doi: 10.1016/0304-4165(73)90320-6. [DOI] [PubMed] [Google Scholar]
  58. van den Berghe G., van Pottelsberghe C., Hers H. G. A kinetic study of the soluble 5'-nucleotidase of rat liver. Biochem J. 1977 Mar 15;162(3):611–616. doi: 10.1042/bj1620611. [DOI] [PMC free article] [PubMed] [Google Scholar]

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