Molecular Probes for Adenosine Receptors

  • K. A. Jacobson

Abstract

High affinity adenosine agonists and antagonists have been developed as radioligands for characterizing adenosine receptors in binding studies. Previous studies have utilized reversibly binding tritiated ligands such as the A1-selective agonists (Table 1) N6-cyclohexyladenosine, 1 (Bruns et al, 1983), and R-N6-(phenylisopropyl)adenosine, 2 (Schwabe and Trost, 1980), or the A1-selective antagonists (Table 2), XAC, 7 (xanthine amine congener, 8-((2-aminoethyl)-aminocarbonylmethyloxyphenyl)-l,3-dipropybcanthine) (Jacobson et al, 1986) and CPX, 6 (l,3-dipropyl-8-cyclopentylxanthine) (Bruns et al, 1987). [3H]CPX has a Kd at rat brain A1 receptors of 0.42 nM and a Ki at A2 receptors of 410 nM. At present, [3H]CPX is the most A1-selective among the commonly used antagonist radioligands. pH]XAC is 60-fold A1-selective in the rat brain and is of nearly the same affinity (Kd = 1.2 nM) as CPX.

Keywords

Adenosine Caffeine Theophylline Biotin Purine 

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References

  1. Barone, S., Churchill, P.C., Jacobson, K.A. (1989) Adenosine receptor prodrugs: towards kidney-selective dialkylxanthines. J. Pharm. Exp. Therap. 250, 79–85.Google Scholar
  2. Barrington, W.W., Jacobson, K.A., and Stiles, G.L. (1989a) Demonstration of distinct agonist and antagonist conformations of the A1 adenosine receptor, J. Biol. Chem., 264, 13157–13164.PubMedGoogle Scholar
  3. Barrington, W.W., Jacobson, K.A., Williams, M., Hutchison, A.J. and Stiles, G.L. (1989b) Identification of the A2 adenosine receptor binding subunit by photoaffinity crosslinking. Proc. Natl. Acad. Sci USA 86, 6572–6576.PubMedCrossRefGoogle Scholar
  4. Bruns, R.F., Daly, J.W. and Snyder, S.H. (1980) Adenosine receptors in brain membranes: binding of N6-cyclohexyl[3H]adenosine and l,3-diethyl-8-pH]phenylxanthine. Proc. Natl. Acad. Sci. U.S.A. 77, 5547–5551.PubMedCrossRefGoogle Scholar
  5. Bruns, R.F., Daly, J.W. and Snyder, S.H. (1983) Adenosine receptor binding: structure-activity analysis generates extremely potent xanthine antagonists. Proc. Natl. Acad. Sci. U.S.A. 80, 2077–2080.PubMedCrossRefGoogle Scholar
  6. Bruns, R.F., Lu, G.H. and Pugsley, T.A. (1986) Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes. Mol. Pharmacol. 29, 331–346.PubMedGoogle Scholar
  7. Bruns, R.F., Fergus, J.H., Badger, E.W., Bristol, J.A., Santay, L.A., Hartman, J.D., Hays, S.J. and Huang, C.C. (1987).Binding of the A1-selective adenosine antagonist 8-cyclopentyl-l,3-dipropylxanthine to rat brain membranes. Naunyn-Schmiedeberg’s Arch. Pharmacol. 335, 59–63.Google Scholar
  8. Choca, J.I., Kwatra, M.M., Hosey, M.M. and Green R.D.(1985) Specific photoaffinity labeling of inhibitory adenosine receptors. Biochem. Biophys. Res. Comm. 131, 115–121.PubMedCrossRefGoogle Scholar
  9. Earl, C.Q., Patel, A., Craig, R.H., Daluge, S.M. and Linden, J.L. (1988) Photoaffinity labeling adenosine A1 receptors with an antagonist 125I-labeled aryl azide derivative of 8-phenylxanthine. J. Med. Chem. 31, 752–756.PubMedCrossRefGoogle Scholar
  10. Fredholm, B.B., Jacobson, K.A., Jonzon, B., Kirk, K.L., Li, Y.O., Daly, J.W. (1987) Evidence that a novel 8-phenyl-substituted xanthine derivative is a cardioselective adenosine receptor antagonist in vivo. J. Cardiovasc. Pharmacol. 9, 396–400.PubMedCrossRefGoogle Scholar
  11. Friessmuth, M., Hausleithner, V., Tuisl, E., Nanoff, C., and Schutz, W. (1987) Naunyn-Schmiedeberg’s Arch. Pharmacol. 335, 438.CrossRefGoogle Scholar
  12. Hofmann, K. and Finn, F.M. (1985) Affinity chromatography of ther insulin receptor based on the avidin-biotin interaction. Ann. N.Y. Acad. Sci. 447, 359–372.PubMedCrossRefGoogle Scholar
  13. Hutchison, A.J., Williams, M. deJesus, R., Oei, H.H., Ghai, G.R., Webb, R.L., Zoganas, H.C., Stone, G.A. and Jarvis, M.F.(1990) 2-Arylalkylamino-adenosine 5′-uronamides: a new class of highly selective adenosine A2 receptor agonists. J. Med. Chem., in press.Google Scholar
  14. Jacobson, K.A., Kirk, K.L., Padgett, W., Daly, J.W. (1985) Probing the adenosine receptor with adenosine and xanthine biotin conjugates. FEBS Lett. 184, 30–35.PubMedCrossRefGoogle Scholar
  15. Jacobson, K.A., Ukena, D., Kirk, K.L., Daly, J.W. (1986) [3H]xanthine amine congener of l,3-dipropyl-8-phenylxanthine: an antagonist radioligand for adenosine receptors. Proc. Natl. Acad. Sci. USA 83, 4089–4093.PubMedCrossRefGoogle Scholar
  16. Jacobson, K.A., Ukena, D., Padgett, W., Kirk, K.L., Daly, J.W. (1987) Molecular probes for extracellular adenosine receptors. Biochem. Pharmacol. 36, 1697–1707.PubMedCrossRefGoogle Scholar
  17. Jacobson, K.A., Barone, S., Kammula, U., Stiles, G.L. (1989a) Electrophilic derivatives of purines as irreversible inhibitors of A1-adenosine receptors. J. Med. Chem. 32, 1043–1051.PubMedCrossRefGoogle Scholar
  18. Jacobson, K.A., Barrington, W.W., Pannell, L.K., Jarvis, M.F., Ji, X.-D., Williams, M., Hutchison, A.J., Stiles, G.L. (1989b) Agonsist-derived molecular probes for A2-adenosine receptors. J. Mol. Recognition, in press.Google Scholar
  19. Jarvis, M.F, Schutz, R., Hutchison, AJ., Do, E., Sills, M.A. and Williams, M.(1989) [3H]CGS 21680, an A2 selective adenosine receptor agonist directly labels A2 receptors in rat brain tissue. J. Pharmacol. Exp. Ther. in press.Google Scholar
  20. Klotz, K.-N., Cristalli, G., Grifantini, M., Vittori, S. and Lohse, M.J.(1985) Photoaffinity labeling of A1-adenosine receptors. J. Biol. Chem. 260, 14659–14664.PubMedGoogle Scholar
  21. Linden, J., Patel, A. and Sadek, S. (1985) [125I]Aminobenzyl adenosine, a new radioligand with improved specific binding to adenosine receptors in heart. Circ. Res. 56, 279–284.PubMedGoogle Scholar
  22. Munshi, R. and Baer, H.P. (1982) Radioiodination of p-hydroxylphenylisopropyl adenosine: development of a new ligand for adenosine receptors. Can. J. Physiol. Pharmacol. 60, 1320–1322.PubMedCrossRefGoogle Scholar
  23. Nakata, H. (1989) Affinity chromatography of A1 adenosine receptors of rat brain membranes. Mol. Pharmacol. 35 780–786.PubMedGoogle Scholar
  24. Olah, M.E., Jacobson, K.A., and Stiles, G.L.(1989) FEBS Letters, in press.Google Scholar
  25. Schwabe, U. and Trost, T. (1980) Characterization of adenosine receptors in rat brain by (-)[3H]N6-phenylisopropyl adenosine Naunyn-Schmiedeberg’s Arch. Pharmacol. 313, 179–187.CrossRefGoogle Scholar
  26. Schwabe, U., Lenschow, V., Ukena, D., Ferry, D.R. and Glossman, H. (1982) [125I]N6-p-hydroxyphenylisopropyl adenosine, a new ligand for Ri receptors. Naunyn-Schmiedeberg’s Arch. Pharmacol. 321, 84–87.CrossRefGoogle Scholar
  27. Seale, T.W., Abla, K.A., Jacobson, K.A., Carney, J.M. Xanthine amine congener of l,3-dipropyl-8-phenylxanthine (XAC): a peripherally-selective adenosine receptor blocking agent. Pharmacol. Biochem. Behav., in press.Google Scholar
  28. Stiles, G.A. and Jacobson, K.A. (1987). A new high affinity iodinated adenosine receptor antagonist as a radioligand/photoaffinity crosslinking probe. Mol. Pharmacol. 32, 184–188.Google Scholar
  29. Stiles, G. A. and Jacobson, K. A. (1988). High affinity acylating antagonists for the A1 adenosine receptor: identification of binding subunit. Mol. Pharmacol. 34, 724–728.PubMedGoogle Scholar
  30. Stiles, G.A., Daly, D.T. and Olsson, R.A. (1985) The A1 adenosine receptor. Identification of the binding subunit by photoaffinity crosslinking. J. Biol. Chem. 260, 10806–10811.PubMedGoogle Scholar
  31. Ukena, D., Jacobson, K.A., Kirk, K.L. and Daly, J.W. (1986) A [3H]amine congener of l,3-dipropyl-8-phenyl xanthine — a new radioligand for A2 adenosine receptors of human platelets. FEBS Lett. 199, 269–274.PubMedCrossRefGoogle Scholar
  32. Yeung, S. M. H. and Green, R. D. (1984) [3H]5’-N-ethylcarboxamide adenosine binds to both Ra and Ri receptors in rat striatum. Naunyn-Schmiedeberg’s Arch. Pharmacol. 325, 218–225.CrossRefGoogle Scholar

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© Springer-Verlag New York Inc. 1990

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  • K. A. Jacobson

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