Purines pp 203-214 | Cite as

Magnesium Ions Exert a Central Role in Integrating Adenosine Receptor Occupancy with the Inhibition of Adenylate Cyclase

  • Siu-Mei Helena Yeung
  • Lynn T. Frame
  • J. Craig Venter
  • Dermot M. F. Cooper
Part of the Satellite Symposia of the IUPHAR 9th International Congress of Pharmacology book series (SSNIC)


The adenosine receptors associated with the adipocyte and brain cortex adenylate cyclase are typical of those neurotransmitter receptors that inhibit the enzyme’s activity in numerous tissues (1). This receptor regulates enzyme activity through a GTP regulatory protein complex (Ni) that is distinct from that which mediates stimulation of the enzyme (Ns) (2–7). The GTP regulatory complex modulates enzyme activity via a GTP hydrolytic cycle involving heterotropic interactions with the receptor and catalytic unit (8–13). Considerable progress has recently been made on characterizing the two types of GTP regulatory complex. Both appear to be comprised of at least three subunits, one of which is unique and two that are common to both complexes. The unique subunit associated with N. can be ADP-ribosylated by islet-activating protein (IAP) a toxin elicited by Bordetella pertussis (7,14,15). At present, the most direct evidence that the IAP substrate is a functional component of Ni mediating hormone inhibition is the demonstration of attenuation of hormonal inhibition by IAP and the reversal of this attenuation by the addition of exogenous (non-treated) IAP substrate (14–16). Such evidence clearly supports a role for the IAP substrate in an Ni complex, although it does not exclude the possibility that other subunits might be required for the promotion of hormonal inhibition.


Adenylate Cyclase Adenosine Receptor Bordetella Pertussis Hormonal Inhibition Affinity State 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Londos, C., Cooper, D.M.F. and Rodbell, M. (1981). Adv. Cyclic. Nucleotide Res. 14, 163–171.PubMedGoogle Scholar
  2. 2.
    Jakobs, K.H. (1979). Mol. Cell. Endocrinol. 16, 147–156.PubMedCrossRefGoogle Scholar
  3. 3.
    Rodbell, M. (1980). Nature 284, 17–22.PubMedCrossRefGoogle Scholar
  4. 4.
    Limbird, L.E. (1981). Biochem. J. 195, 1–13.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Cooper, D.M.F. (1982). FEBS Lett. 138, 157–163.PubMedCrossRefGoogle Scholar
  6. 6.
    Hildebrandt, J.D., Sekura, R.D., Codina, J., Iyengar, R., Manclark, C.R. and Bimbaumer, L. (1983). Nature 302:706–709.PubMedCrossRefGoogle Scholar
  7. 7.
    Gilman, A.G. (1984). Cell 36,577–579.PubMedCrossRefGoogle Scholar
  8. 8.
    Cassel, D. and Selinger, Z. (1976). Biochem. Biophys. Acta 452, 538–551.Google Scholar
  9. 9.
    Ross, E.M. and Gilman, A.G. (1980). Ann. Rev. Biochem. 49, 533–564.Google Scholar
  10. 10.
    Aktories, K. and Jakobs, K.H. (1981). FEBS Lett. 130, 235–238.PubMedCrossRefGoogle Scholar
  11. 11.
    Koski, G. and Klee, W.A. (1981). Proc. Natl. Acad. Sci. USA 78 4185–4189.Google Scholar
  12. 12.
    Aktories, K., Schultz, G. and Jakobs, K.H. (1982). Mol. Pharmacol. 21, 336–342.PubMedGoogle Scholar
  13. 13.
    Michel, T. and Lefkowitz, R.J. (1982). J. Biol. Chem. 257, 13557–13563.Google Scholar
  14. 14.
    Katada, T. and Ui, M. (1982). Proc. Nat! Acad. Sci. USA 79, 3129–3133.Google Scholar
  15. 15.
    Katada, T. and Ui, M. (1982). J. Biol. Chem. 257, 7210–7216.Google Scholar
  16. 16.
    Katada, T., Bokoch, G.M., Northup, J.K., Ui, M. and Gilman, A.G. (1984). J. Biol. Chem. 259, 3568–3577.Google Scholar
  17. 17.
    Brandt, D.R., Asano, T., Pedersen, S.E. and Ross, E.M. (1983). Biochemistry 22, 4357–4362.PubMedCrossRefGoogle Scholar
  18. 18.
    Caron, M.G., Cerione, R.A., Benovic, J.L., Strulovici, B., Staniszewski, C., Lefkowitz, R.J., Codina-Salada, J. and Bimbaumer, L., (in press) Adv. Cyclic, Nucleotide Res.Google Scholar
  19. 19.
    Tsai, B.S. and Lefkowitz, R.J. (1979). Mol. Pharmacol. 61–68.Google Scholar
  20. 20.
    U’Prichard, D.C. and Snyder, S.H. (1980). J. Neurochem. 34, 385–394.PubMedCrossRefGoogle Scholar
  21. 21.
    Yeung, S.-M.H. and Green R.D. (1983). J. Biol. Chem. 258, 2334–2339.Google Scholar
  22. 22.
    Codina,.1, Hildebrandt, J., Iyengar, R., Bimbaumer, L., Sekura, R.D. and Manclark, C.R. (1983). Proc. Natl. Acad. Sci. USA 80, 4276–4280.Google Scholar
  23. 23.
    Cooper, D.M.F., Schlegel, W., Lin, M.C. and Rodbell, M. (1979). J. Biol. Chem. 254, 8927–8930.Google Scholar
  24. 24.
    Jakobs, K.H. and Aktories, K. (1981). Biochem. Biophys. Acta. 676, 51–58.Google Scholar
  25. 25.
    Hoffman, B.B., Yim, S., Tsai, B.S. and Lefkowitz, R.J. (1981). Biochem. Biophys. Res. Commun. 100,724–731.Google Scholar
  26. 26.
    Bockaert, J., Cantau, B. and Sebben-Perez, M. (in press) Mol. Pharm acol.Google Scholar
  27. 27.
    Schramm, M. and Naim, E. (1970). J. Biol. Chem. 245, 3225–3231.Google Scholar
  28. 28.
    Schramm, M. (1976). J. Cyc. Nuc. Res. 2 347–358.Google Scholar
  29. 29.
    Yeung, S-M. H., Fossom, L.H., Gill, D.L. and Cooper, D.M.F. submitted.Google Scholar
  30. 30.
    Trost, T. and Schwabe, U. (1981). Mol. Pharrnacot, 19, 228–235.Google Scholar
  31. 31.
    MlI1son, P.J. and Rodbard, D. (1980). Anal. Biochem. 107, 220–239.Google Scholar
  32. 32.
    Neer, E.J. (1976). J. BioI. Chern. 249, 6527–6532.Google Scholar
  33. 33.
    Kilpatrick, B.F. and Caron, M.G. (1983). J. BioI. Chern. 258, 13528–13534.Google Scholar
  34. 34.
    Lew, J.Y. and Goldstein, M. (1984). J. Neurochem. 42, 1298–1305.Google Scholar
  35. 35.
    Harmon, J. T., Kempner, E.S. and Kahn, C.R. (1981). J. Biol, Chern. 256, 7719–7722.Google Scholar
  36. 36.
    Kincaid, R.L., Kempner, E.S., Manganiello, V.C., Osbourne, J.C. and Vaughan, M. (1981). J. arer, Chern. 256, 11351–11355.Google Scholar
  37. 37.
    Avissars, S., Amitai, G. and Sokolovsky, M. (1983). Proc. Natl, Acad. Sci. USA 80, 156–159.Google Scholar
  38. 38.
    Chang, HW. and Bock, E. (1977) Biochemistry 16, 4513–4520PubMedCrossRefGoogle Scholar
  39. 39.
    Venter, C. (1984). In: Neurotransmitter Receptors: Mechanisms of Action and Regulation. S. Kito, K. Kuriyama, HI. Yamamura and R.W. Olsen (eds) Plenum Press.Google Scholar

Copyright information

© The Contributors 1985

Authors and Affiliations

  • Siu-Mei Helena Yeung
  • Lynn T. Frame
  • J. Craig Venter
  • Dermot M. F. Cooper

There are no affiliations available

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