Home LiteratureArticle Details
PMID: 3800923 Published · ppublish English Journal Article

How does dipyridamole elevate extracellular adenosine concentration? Predictions from a three-compartment model of adenosine formation and inactivation.

The Biochemical journal ·Vol. 237 ·No. 3 ·1986-08-01 ·Pages 845-51

Newby AC

Abstract

Steady-state mathematical models are developed according to which adenosine is formed in the cytoplasm of a group of cells, arises in the extracellular space via the symmetric nucleoside transporter and is inactivated in the adenosine forming cells and after rate-limiting transport into other cell-types. Dipyridamole increases the Km and Vmax. of the transporter symmetrically with respect to influx and efflux. Models incorporating differing degrees of compartmentation are used to predict intracellular and extracellular adenosine concentration as a function of dipyridamole concentration and adenosine formation rate. The vasodilator action of dipyridamole is explained since it is predicted to elevate interstitial fluid adenosine concentrations at all rates of adenosine formation provided that washout of the interstitial compartment is restricted.

MeSH Terms
Adenosine/antagonists & inhibitors,metabolism Adenosine Deaminase/metabolism Adenosine Kinase/metabolism Biological Transport/drug effects Cell Compartmentation/drug effects Dipyridamole/pharmacology Extracellular Space/drug effects,metabolism Models, Biological Nucleosides/antagonists & inhibitors
Chemicals
Nucleosides Dipyridamole Adenosine Kinase Adenosine Deaminase Adenosine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Newby A C
References (32)
32 references, click to expand
  1. Inhibition of adenosine uptake in human erythrocytes by adenosine-5'-carboxamides, xylosyladenine, dipyridamole, hexobendine, and p-nitrobenzylthioguanosine.
    Biochem Pharmacol. 1978;27(18):2191-7 PMID: 728171
  2. Uptake and metabolism of adenosine by pig aortic endothelial and smooth-muscle cells in culture.
    Biochem J. 1978 Feb 15;170(2):265-71 PMID: 637842
  3. Specific determination of dipyridamole in serum by high-performance liquid chromatography.
    J Chromatogr. 1979 Jan 1;162(1):98-103 PMID: 762215
  4. Adenosine transport and metabolism in mouse leukemia cells and in canine thymocytes and peripheral blood leukocytes.
    J Cell Physiol. 1979 Nov;101(2):173-200 PMID: 315949
  5. A common basis for inhibition of nucleoside transport by dipyridamole and nitrobenzylthioinosine?
    Mol Pharmacol. 1980 Jul;18(1):40-4 PMID: 7412763
  6. Different sites of adenosine formation in the heart.
    Am J Physiol. 1981 Jun;240(6):H963-70 PMID: 6264801
  7. Role of S-adenosylhomocysteine hydrolase in adenosine metabolism in mammalian heart.
    Biochem J. 1981 Apr 15;196(1):65-70 PMID: 7306081
  8. Benzodiazepine inhibition of site-specific binding of nitrobenzylthioinosine, an inhibitor of adenosine transport.
    Life Sci. 1981 Nov 23;29(21):2207-14 PMID: 6119591
  9. Species differences in nucleoside transport. A study of uridine transport and nitrobenzylthioinosine binding by mammalian erythrocytes.
    Biochem J. 1982 Oct 15;208(1):83-8 PMID: 7159400
  10. Release of two vasodilators, adenosine and prostacyclin, from isolated rabbit hearts during controlled hypoxia.
    J Physiol. 1983 Jul;340:487-501 PMID: 6350560
  11. 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):317-23 PMID: 6604525
  12. The mechanism of adenosine production in rat polymorphonuclear leucocytes.
    Biochem J. 1983 Aug 15;214(2):325-30 PMID: 6311180
  13. Theoretical analysis of adenosine release from cardiac tissue as influenced by transport inhibitors.
    Can J Physiol Pharmacol. 1983 Aug;61(8):946-9 PMID: 6627134
  14. Nucleoside transport in cultured mammalian cells. Multiple forms with different sensitivity to inhibition by nitrobenzylthioinosine or hypoxanthine.
    Biochim Biophys Acta. 1984 Jun 13;773(1):39-52 PMID: 6733097
  15. Theophylline antagonizes cardiovascular responses to dipyridamole in man without affecting increases in plasma adenosine.
    Acta Physiol Scand. 1984 Jun;121(2):165-71 PMID: 6475546
  16. Role of extracellular and intracellular adenosine in the attenuation of catecholamine evoked responses in guinea pig heart.
    J Mol Cell Cardiol. 1984 Sep;16(9):813-22 PMID: 6092651
  17. Effects of dipyridamole on myocardial adenosine and active hyperemia.
    Am J Physiol. 1984 Nov;247(5 Pt 2):H804-10 PMID: 6496762
  18. Inward fluxes of adenosine in erythrocytes and cultured cells measured by a quenched-flow method.
    Biochem J. 1984 Dec 15;224(3):1001-8 PMID: 6525168
  19. Dipyridamole decreases glomerular filtration in the sodium-depleted dog. Evidence for mediation by intrarenal adenosine.
    Circ Res. 1985 Feb;56(2):242-51 PMID: 3882259
  20. Modeling of transendothelial transport.
    Fed Proc. 1985 Jul;44(10):2623-6 PMID: 4007183
  21. The mechanism of adenosine release from hypoxic rat liver cells.
    Br J Pharmacol. 1985 Jun;85(2):441-6 PMID: 4027478
  22. Adenosine formation and release from neonatal-rat heart cells in culture.
    Biochem J. 1985 Aug 1;229(3):799-805 PMID: 2996488
  23. Studies on the mode of action of hexobendine, a prospective anti-anginal drug.
    Br J Pharmacol. 1969 Sep;37(1):272-82 PMID: 5343351
  24. Inhibition of coronary vasodilating action of dipyridamole and adenosine by aminophylline in the dog.
    Circ Res. 1970 Jun;26(6):743-52 PMID: 4987265
  25. The possible role of adenosine in the coronary dilator action of some pyrimidopyrimidines and pteridines.
    Br J Pharmacol. 1970 Jun;39(2):287-95 PMID: 5425274
  26. Influence of dipyridamol (Persantin) on myocardial adenosine metabolism.
    J Mol Cell Cardiol. 1970 Mar;1(1):23-38 PMID: 5520352
  27. Cerebral and coronary vascular effects of a symmetrical N,N'-disubstituted hexahydrodiazepine.
    J Pharmacol Exp Ther. 1972 Jun;181(3):522-8 PMID: 5033017
  28. Inhibition of hypoxia-induced rise in adenosine release and flow by coronary dilators.
    Cardiology. 1971;56(1):107-13 PMID: 5152736
  29. 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):6372-8 PMID: 977576
  30. 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):877-88 PMID: 137322
  31. Compartmentation of cardiac adenine nucleotides and formation of adenosine.
    Pflugers Arch. 1976 Dec 28;367(2):129-35 PMID: 189285
  32. The control of the metabolism and the hormonal role of adenosine.
    Essays Biochem. 1978;14:82-123 PMID: 365523
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
Published
1986-08-01
Pages
845-51
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1147065
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com