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Adenosine Receptors in the Heart

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Book cover Regulation of Coronary Blood Flow

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Summary

A1 and A2 adenosine receptors (A1AR, A2AR) mediate the biological actions of this nucleoside. The ligand-binding peptide of the A1AR has an Mr of 35–38 kd and that of the A2AR an Mr of 45 kd. Both are glycoproteins. Alkylxanthines, such as theophylline, competitively inhibit ligand binding at both receptors. GTP-binding transduction proteins couple the receptors to their effectors, Gi (and Go?) for the A1AR and Gs for the A2AR. Effectors which are known to be coupled to cardiac A1ARs include adenylate cyclase (inhibition), muscarinic K+ channels (activation), and ATP-sensitive K+ channels (activation). A1ARs coupled to phospholipase C apparently do not occur in the heart. Stimulation of adenylate cyclase is the only known effect of A2AR activation. Adenosine, formed in the heart and acting through A1ARs coupled to K+ channels, slows the rate of SA node firing, retards conduction through the AV node, and reduces the force of atrial but not ventricular contraction. Acting through A1ARs coupled to adenylate cyclase, adenosine antagonizes the cardiostimulatory actions of catecholamines and other agonists that stimulate cyclic AMP production. A2ARs in the coronary arteries mediate vasodilation. One source of adenosine is cytosolic AMP, linked through myokinase to the cytosolic ATP phosphorylation potential, an index of cellular energy state. Adenosine from this source is thought to couple coronary blood flow rate to the cellular energy state, thus constituting the metabolic component of coronary flow control. The actions of adenosine at cardiac muscle A1ARs tend to reduce energy consumption, whereas the action at coronary A2ARs increases energy supply. In concert, these actions are cardioprotective.

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References

  1. Schrader J, Gerlach E (1977) Compartmentation of cardiac adenine nucleotides and formation of adenosine. Pflügers Arch 367:129–135.

    Article  Google Scholar 

  2. Olsson RA, Saito D, Steinhart CR (1982) Compartmentalization of the adenosine pool of dog and rat hearts. Circ Res 50:617–626.

    Article  PubMed  CAS  Google Scholar 

  3. Berne RM, Rubio R (1974) Adenine nucleotide metabolism in the heart. Circ Res 34/35(Suppl II):III109–III120.

    Google Scholar 

  4. Hershfield MS, Kredich NM (1978) S-adenosylhomocysteine hydrolase is an adenosine-binding protein: A target for adenosine toxicity. Science 202:757–760.

    Article  PubMed  CAS  Google Scholar 

  5. Ueland PM (1982) Pharmacological and biochemical aspects of S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase. Pharmacol Rev 34:223–253.

    PubMed  CAS  Google Scholar 

  6. Deussen A, Borst M, Schrader S (1988) Formation of S-adenosylhomocysteine in the heart. I. An index of free intracellular adenosine. Circ Res 63:240–249.

    Article  PubMed  CAS  Google Scholar 

  7. Saito D, Steinhart CR, Nixon DG, Olsson RA (1981) Intracoronary adenosine deaminase reduces canine myocardial reactive hyperemia. Circ Res 47:875–882.

    Article  Google Scholar 

  8. Kroll K, Feigl EO (1985) Adenosine is unimportant in controlling coronary blood flow in unstressed dog hearts. Am J Physiol 249:H1176–H1187.

    PubMed  CAS  Google Scholar 

  9. Dole WP, Yamada N, Bishop VS, Olsson RA (1985) Role of adenosine in coronary blood flow regulation after reductions in coronary pressure. Circ Res 56:517–524.

    Article  PubMed  CAS  Google Scholar 

  10. Hanley FL, Grattan MT, Stevens MB, Hoffman JIE (1986) Role of adenosine in coronary autoregulation. Am J Physiol 250:H558–H566.

    PubMed  CAS  Google Scholar 

  11. Gewirtz H, Olsson RA, Brautigan DL, Brown PR, Most AS (1986) Adenosine’s role in regulating basal coronary arteriolar tone. Am J Physiol 250:H1030–H1036.

    PubMed  CAS  Google Scholar 

  12. Bünger R, Haddy FJ, Gerlach E (1975) Coronary responses to dilating substances and competitive inhibition by theophylline in the isolated perfused guinea pig heart. Pflügers Arch 358:213–224.

    Article  PubMed  Google Scholar 

  13. Schrader J, Haddy FJ, Gerlach E (1976) Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow autoregulation and reactive hyperemia. Pflügers Arch 369:1–6.

    Article  Google Scholar 

  14. Olsson RA, Khouri EM, Bedynek JL Jr, McLean J (1979) Coronary vasoactivity of adenosine in the conscious dog. Circ Res 45:468–478.

    Article  PubMed  CAS  Google Scholar 

  15. Jarvis SM (1987) Kinetic and molecular properties of nucleoside transporters in mammalian cells. In: Gerlach E, Becker BF (eds) Topics and perspectives in adenosine research. Springer-Verlag, Berlin, pp 102–116.

    Chapter  Google Scholar 

  16. Itoh R (1981) Purification and some properties of cytosol 5′-nucleotidase from rat liver. Biochem Biophys Acta 657:402–410.

    Article  PubMed  CAS  Google Scholar 

  17. Newby AC (1988) The pigeon heart 5′-nucleotidase responsible for ischaemia-induced adenosine formation. Biochem J 253:123–130.

    PubMed  CAS  Google Scholar 

  18. Newby AC, Worku Y, Meghji P (1985) Adenosine formation: Evidence for a direct biochemical link with energy metabolism. Adv Myocardiol 6:273–284.

    PubMed  CAS  Google Scholar 

  19. Bünger R, Soboll S (1986) Cytosolic adenylates and adenosine release in perfused working heart. Comparison on whole tissue with cytosolic nonaqueous fractionation analyses. Eur J Biochem 159:203–213.

    Article  PubMed  Google Scholar 

  20. Imai S, Chin W-P, Jin H, Nakazawa M (1989) Production of AMP and adenosine in the interstitial fluid compartment of the isolated perfused normoxic guinea pig heart. Pflügers Arch 414:443–449.

    Article  PubMed  CAS  Google Scholar 

  21. Bünger R, Hartman DA, Mallet RT (1990) Radiochemical evidence for free insterstitial 5′-AMP in isolated physiologically performing working heart. In: Jacobson KA, Daly JW, Manganiello V (eds) Purines in cellular signaling: Targets for new drugs. Springer-Verlag, Berlin, pp 388–389.

    Google Scholar 

  22. Schrader S, Borst MM, Kelm M, Bading B, Burrig KF (1990) Formation of adenosine in the heart from extracellular adenine nucleotides. Jacobson KA, Daly JW, Manganiello V (eds) Purines in cellular signaling: Targets for new drugs. Springer-Verlag, Berlin, pp 33–40.

    Chapter  Google Scholar 

  23. Olsson RA, Bünger R (1987) Metabolic control of coronary blood flow. Progr Cardiovasc Dis 29:369–387.

    Article  CAS  Google Scholar 

  24. Van Calcker D, Müller D, Hamprecht B (1979) Adenosine regulates via two different receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem 33:999–1005.

    Article  Google Scholar 

  25. Londos C, Cooper DMF, Wolff J (1980) Subclasses of external adenosine receptors. Proc Natl Acad Sci USA 77:2551–2554.

    Article  PubMed  CAS  Google Scholar 

  26. Smellie FW, Daly JW, Dunwiddie TV, Hoffer BJ (1979) The dextro-and levorotatory isomers of N-phenylisopropyladenosine: Stereospecific effects on cyclic AMP-formation and evoked synaptic responses in brain slices. Life Sci 25:1739–1748.

    Article  PubMed  CAS  Google Scholar 

  27. Nakata H (1989) Purification of A1 adenosine receptor from rat brain membranes. J Biol Chem 264:16545–16551.

    PubMed  CAS  Google Scholar 

  28. Nakata H (1989) 5′-N-ethylcarboxamido[3H]adenosine binding sites of mouse P815 mastocytoma cell membranes: Solubilization and partial purification by affinity chromatography. J Biochem 105:700–704.

    PubMed  CAS  Google Scholar 

  29. Drury AN, Szent-Györgi A (1929) The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J Physiol (Lond) 68:213–237.

    CAS  Google Scholar 

  30. Belardinelli L, Linden J, Berne RM (1989) The cardiac effects of adenosine. Progr Cardiovasc Dis 32:73–97.

    Article  CAS  Google Scholar 

  31. Belardinelli L, Isenberg G (1983) Isolated atrial myocytes: Adenosine and acetylcholine increase potassium conductance. Am J Physiol 244:H734–H737.

    PubMed  CAS  Google Scholar 

  32. Jochem G, Nawrath H (1983) Adenosine activates a potassium conductance in guinea-pig atrial heart muscle. Experimentia 39:1347–1349.

    Article  CAS  Google Scholar 

  33. Kurachi Y, Nakajima T, Sugimoto T (1986) On the mechanism of activation of muscarinic K+ channels by adenosine in isolated atrial cells: Involvement of GTP-binding proteins. Pflügers Arch 407:264–274.

    Article  PubMed  CAS  Google Scholar 

  34. Clemo HF, Belardinelli L (1986) Effect of adenosine on atrioventricular conduction. I: Site and characterization of adenosine action in the guinea pig atrioventricular node. Circ Res 59:427–436.

    Article  PubMed  CAS  Google Scholar 

  35. Szentmiklósi AJ, Ńemeth JM, Szegi J, Papp JG, Szekeres L (1980) Effect of adenosine in sinoatrial and ventricular automaticity of the guinea pig. Naunyn Schmiedebergs Arch Pharmacol 311:147–149.

    Article  PubMed  Google Scholar 

  36. Kirsch GE, Codina J, Birnbaumer L, Brown AM (1990) Coupling of ATP-sensitive K+ channels to A1 receptors by G proteins in rat ventricular myocytes. Am J Physiol 259:H820–H826.

    PubMed  CAS  Google Scholar 

  37. Schrader J, Baumann G, Gerlach E (1977) Adenosine as inhibitor of myocardial effects of catecholamines. Pflügers Arch 372:29–35.

    Article  PubMed  CAS  Google Scholar 

  38. Dobson JG Jr (1983) Mechanism of adenosine inhibition of catecholamine-induced responses in heart. Circ Res 52:151–160.

    Article  PubMed  CAS  Google Scholar 

  39. Seitelberger R, Schütz W, Schlappack O, Raberger G (1984) Evidence against the adenosine-catecholamine antagonism under in vivo conditions. Naunyn Schmiedebergs Arch Pharmacol 325:234–239.

    Article  PubMed  CAS  Google Scholar 

  40. Henrich M, Piper HM, Schrader J (1987) Evidence for adenylate cyclase-coupled A1-adenosine receptors on ventricular cardiomyocytes from adult rat and dog heart. Life Sci 41:2381–2388.

    Article  PubMed  CAS  Google Scholar 

  41. Romano FD, Macdonald SG, Dobson JG Jr (1989) Adenosine receptor coupling to adenylate cyclase of rat ventricular myocyte membranes. Am J Physiol 257:H1088–H1095.

    PubMed  CAS  Google Scholar 

  42. Behnke N, Muller W, Neumann J, Schmitz W, Scholz H, Stein B (1990) Differential antagonism by l,3-dipropylxanthine-8-cyclopentylxanthine and 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo(1,5-c)quinazolin-5-imine of two effects of adenosine derivatives in the presence of isoprenaline on contractile response and cyclic AMP content in cardiomyocytes. Evidence for the coexistence of A1-and A2-adenosine receptors on cardiomyocytes. J Pharmacol Exp Ther 254:1017–1023.

    PubMed  CAS  Google Scholar 

  43. Kusachi S, Thompson RD, Olsson RA (1983) Ligand selectivity of dog coronary adenosine receptor resembles that of adenylate cyclase stimulatory (Ra) receptors. J Pharmacol Exp Ther 227:316–321.

    PubMed  CAS  Google Scholar 

  44. Ramagopal MV, Chitwood RWJ, Mustafa SJ (1988) Evidence for an A2 adenosine receptor in human coronary arteries. Eur J Pharmacol 151:483–486.

    Article  PubMed  CAS  Google Scholar 

  45. Nees S, Gerbes AL, Willershausen-Zonnchen B, Gerlach E (1985) The coronary endothelium: A highly active metabolic barrier for adenosine. Basic Res Cardiol 80:515–529.

    Article  PubMed  CAS  Google Scholar 

  46. Rubanyi G, Vanhoutte PM (1985) Endothelium removal decreases relaxations of canine coronary arteries caused by β-adrenergic agonists and adenosine. J Cardio-vasc Pharmacol 7:139–144.

    Article  CAS  Google Scholar 

  47. Kwan YW, Wadsworth RM, Kane KA (1989) Hypoxia-and endothelium-mediated changes in the pharmacological responsiveness of circumflex coronary artery rings from sheep. Br J Pharmacol 96:857–863.

    Article  PubMed  CAS  Google Scholar 

  48. Des Rosiers C, Nees S (1987) Functional evidence for the presence of adenosine A2-receptors in cultured coronary endothelial cells. Naunyn Schmiedebergs Arch Pharmacol 336:94–98.

    PubMed  Google Scholar 

  49. Newman WH, Becker BF, Heier M, Nees S, Gerlach E (1988) Endothelium-mediated coronary dilatation by adenosine does not depend on endothelial adenylate cyclase activation: Studies in isolated guinea pig hearts. Pflügers Arch 413:1–7.

    Article  PubMed  CAS  Google Scholar 

  50. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84:9265–9269.

    Article  PubMed  CAS  Google Scholar 

  51. Kahn MT, Furchgott RF (1987) Similarities of behavior of nitric oxide (NO) and endothelium-derived relaxing factor in a perfusion cascade bioassay system. Fed Proc 46:385.

    Google Scholar 

  52. Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium—derived relaxing factor. Nature 327:524–526.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, University of South Florida, Tampa, FL, 33612, USA

    Masayuki Ueeda & Ray A. Olsson

  2. Department of Biochemistry and Molecular Biology, University of South Florida, Tampa, FL, 33612, USA

    Ray A. Olsson

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  1. Masayuki Ueeda
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  2. Ray A. Olsson
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Editors and Affiliations

  1. Department of Medical Information Sciences, Osaka University Hospital, Osaka, 553, Japan

    Michitoshi Inoue M.D., Ph.D. (Professor) (Professor)

  2. The First Department of Medicine, Osaka University School of Medicine, Osaka, 553, Japan

    Masatsugu Hori M.D., Ph.D. (Assistant Professor) (Assistant Professor)

  3. Department of Pharmacology, Niigata University School of Medicine, Niigata, 951, Japan

    Shoichi Imai M.D., Ph.D. (Professor) (Professor)

  4. Department of Physiology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA

    Robert M. Berne M.D. (Alumni Professor) (Alumni Professor)

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© 1991 Springer Japan

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Ueeda, M., Olsson, R.A. (1991). Adenosine Receptors in the Heart. In: Inoue, M., Hori, M., Imai, S., Berne, R.M. (eds) Regulation of Coronary Blood Flow. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68367-4_10

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  • DOI: https://doi.org/10.1007/978-4-431-68367-4_10

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68369-8

  • Online ISBN: 978-4-431-68367-4

  • eBook Packages: Springer Book Archive

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