Abstract
The incorporation of [3H]adenosine (10 microM) into neonatal-rat heart cell nucleotides was inhibited in a concentration-dependent manner, such that 50% inhibition was obtained with 0.75 microM-dipyridamole, 0.26 microM-hexobendine or 0.22 microM-dilazep. Adenosine formation was accelerated 2.5-fold to 2.1 +/- 0.3 nmol/10(7) cells in 10 min when cells were incubated with a combination of 30 mM-2-deoxyglucose and 2 micrograms of oligomycin/ml. Of the newly formed adenosine, 6 +/- 2% was in the cells. Dipyridamole, hexobendine or dilazep (10 microM) increased the amount of adenosine in the cells and decreased that in the medium such that 45-50% of the newly formed adenosine was in the cells. Antibodies which inhibited ecto-5'-nucleotidase by 98.7 +/- 0.3% did not alter the rate of adenosine formation or its distribution between cells and medium. We conclude that adenosine was formed in the cytoplasm during catabolism of cellular ATP and was released via the dipyridamole-sensitive symmetric nucleoside transporter.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arch J. R., Newsholme E. A. The control of the metabolism and the hormonal role of adenosine. Essays Biochem. 1978;14:82–123. [PubMed] [Google Scholar]
- 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]
- BERNE R. M. Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. Am J Physiol. 1963 Feb;204:317–322. doi: 10.1152/ajplegacy.1963.204.2.317. [DOI] [PubMed] [Google Scholar]
- Bailyes E. M., Newby A. C., Siddle K., Luzio J. P. Solubilization and purification of rat liver 5'-nucleotidase by use of a zwitterionic detergent and a monoclonal-antibody immunoadsorbent. Biochem J. 1982 Apr 1;203(1):245–251. doi: 10.1042/bj2030245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Degenring F. H., Curnish R. R., Rubio R., Berne R. M. Effect of dipyridamole on myocardial adenosine metabolism and coronary flow in hypoxia and reactive hyperemia in the isolated perfused guinea pig heart. J Mol Cell Cardiol. 1976 Nov;8(11):877–888. doi: 10.1016/0022-2828(76)90070-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Dornand J., Bonnafous J. C., Gavach C., Mani J. C. 5'-Nucleotidase-facilitated adenosine transport by mouse lymphocytes. Biochimie. 1979;61(8):973–977. doi: 10.1016/s0300-9084(79)80249-7. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Forrester T., Williams C. A. Release of adenosine triphosphate from isolated adult heart cells in response to hypoxia. J Physiol. 1977 Jun;268(2):371–390. doi: 10.1113/jphysiol.1977.sp011862. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Frick G. P., Lowenstein J. M. Vectorial production of adenosine by 5'-nucleotidase in the perfused rat heart. J Biol Chem. 1978 Feb 25;253(4):1240–1244. [PubMed] [Google Scholar]
- HARARY I., FARLEY B. In vitro studies on single beating rat heart cells. I. Growth and organization. Exp Cell Res. 1963 Feb;29:451–465. doi: 10.1016/s0014-4827(63)80008-7. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- KISSANE J. M., ROBINS E. The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem. 1958 Jul;233(1):184–188. [PubMed] [Google Scholar]
- Knabb R. M., Gidday J. M., Ely S. W., Rubio R., Berne R. M. Effects of dipyridamole on myocardial adenosine and active hyperemia. Am J Physiol. 1984 Nov;247(5 Pt 2):H804–H810. doi: 10.1152/ajpheart.1984.247.5.H804. [DOI] [PubMed] [Google Scholar]
- Kolassa N., Pfleger K. Adenosine uptake by erythrocytes of man, rat and guinea-pig and its inhibition by hexobendine and dipyridamole. Biochem Pharmacol. 1975 Jan 1;24(1):154–156. doi: 10.1016/0006-2952(75)90331-7. [DOI] [PubMed] [Google Scholar]
- Kolassa N., Pfleger K., Träm M. Species differences in action and elimination of adenosine after dipyridamole and hexobendine. Eur J Pharmacol. 1971;13(3):320–325. doi: 10.1016/0014-2999(71)90221-4. [DOI] [PubMed] [Google Scholar]
- Kukovetz W. R., Pöch G. Inhibition of hypoxia-induced rise in adenosine release and flow by coronary dilators. Cardiology. 1971;56(1):107–113. doi: 10.1159/000169350. [DOI] [PubMed] [Google Scholar]
- Kübler W., Spieckermann P. G., Bretschneider H. J. Influence of dipyridamol (Persantin) on myocardial adenosine metabolism. J Mol Cell Cardiol. 1970 Mar;1(1):23–38. doi: 10.1016/0022-2828(70)90026-x. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Mustafa S. J., Berne R. M., Rubio R. Adenosine metabolism in cultured chick-embryo heart cells. Am J Physiol. 1975 May;228(5):1474–1478. doi: 10.1152/ajplegacy.1975.228.5.1474. [DOI] [PubMed] [Google Scholar]
- Mustafa S. J. Effects of coronary vasodilator drugs on the uptake and release of adenosine in cardiac cells. Biochem Pharmacol. 1979 Sep 1;28(17):2617–2624. doi: 10.1016/0006-2952(79)90037-6. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Newby A. C. Role of adenosine deaminase, ecto-(5'-nucleotidase) and ecto-(non-specific phosphatase) in cyanide-induced adenosine monophosphate catabolism in rat polymorphonuclear leucocytes. Biochem J. 1980 Mar 15;186(3):907–918. doi: 10.1042/bj1860907. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Paddle B. M., Burnstock G. Release of ATP from perfused heart during coronary vasodilatation. Blood Vessels. 1974;11(3):110–119. doi: 10.1159/000158005. [DOI] [PubMed] [Google Scholar]
- Paterson A. R., Kolassa N., Cass C. E. Transport of nucleoside drugs in animal cells. Pharmacol Ther. 1981;12(3):515–536. doi: 10.1016/0163-7258(81)90096-6. [DOI] [PubMed] [Google Scholar]
- Pearson J. D., Carleton J. S., Gordon J. L. Metabolism of adenine nucleotides by ectoenzymes of vascular endothelial and smooth-muscle cells in culture. Biochem J. 1980 Aug 15;190(2):421–429. doi: 10.1042/bj1900421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pearson J. D., Gordon J. L. Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides. Nature. 1979 Oct 4;281(5730):384–386. doi: 10.1038/281384a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Seraydarian M. W., Sato E., Savageau M., Harary I. In vitro studies of beating heart cells in culture. XII. The utilization of ATP and phosphocreatine in oligomycin and 2-deoxyglucose inhibited cells. Biochim Biophys Acta. 1969 Jun 24;180(2):264–270. doi: 10.1016/0005-2728(69)90113-3. [DOI] [PubMed] [Google Scholar]
- 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]
- Turnheim K., Plank B., Kolassa N. Inhibition of adenosine uptake in human erythrocytes by adenosine-5'-carboxamides, xylosyladenine, dipyridamole, hexobendine, and p-nitrobenzylthioguanosine. Biochem Pharmacol. 1978;27(18):2191–2197. doi: 10.1016/0006-2952(78)90076-x. [DOI] [PubMed] [Google Scholar]
- Verma A., Marangos P. J. Nitrobenzylthioinosine binding in brain: an interspecies study. Life Sci. 1985 Jan 21;36(3):283–290. doi: 10.1016/0024-3205(85)90071-2. [DOI] [PubMed] [Google Scholar]
- Williams E. F., Barker P. H., Clanachan A. S. Nucleoside transport in heart: species differences in nitrobenzylthioinosine binding, adenosine accumulation, and drug-induced potentiation of adenosine action. Can J Physiol Pharmacol. 1984 Jan;62(1):31–37. doi: 10.1139/y84-005. [DOI] [PubMed] [Google Scholar]
- 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]
- van den Berghe G., Bronfman M., Vanneste R., Hers H. G. The mechanism of adenosine triphosphate depletion in the liver after a load of fructose. A kinetic study of liver adenylate deaminase. Biochem J. 1977 Mar 15;162(3):601–609. doi: 10.1042/bj1620601. [DOI] [PMC free article] [PubMed] [Google Scholar]
