Advertisement

A Central Role for Magnesium in the Regulation of Inhibitory Adenosine Receptors

  • Dermot M. F. Cooper
  • Siu-Mei Helena Yeung
  • Edward Perez-Reyes
  • Linda H. Fossom
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 160)

Abstract

Many adenylate cyclase systems are being recognized to be subject to both stimulation and inhibition of activity, which is mediated by distinct sets of receptors (1,2). Evidence is accumulating that distinct GTP regulatory proteins are associated with both classes of receptor, although it is not clear whether the GTP regulatory proteins are discrete or part of a large complex. The GTP regulatory proteins serve two major functions: firstly, they transmit the signal of receptor occupancy into either an increase or a decrease in catalytic activity; secondly, they regulate binding of effectors to their receptors (3). The ability to measure these two functions separately uncovers anomalies in our understanding of the communication between receptor, GTP regulatory protein and catalytic unit. Discrepancies are generally encountered between the properties of receptors when judged from the regulation of cyclase activity, compared with their properties as judged by guanine nucleotide regulation of receptor binding. This is particularly apparent in the case of receptors which mediate inhibition of adenylate cyclase. The non-hydrolyzable guanine nucleotide analogues are as effective as GTP at regulating receptor binding; these analogues also promote a characteristic transient inhibition of activity, although they are ineffective in the promotion of receptor-mediated inhibition of activity (1,2).

Keywords

Adenylate Cyclase Adenosine Receptor Guanine Nucleotide Scatchard Analysis Sodium Cholate 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    D. M. F. Cooper, Bimodal regulation of adenylate cyclase, FEBS Lett. 138: 157 (1982).CrossRefGoogle Scholar
  2. 2.
    K. H. Jakobs, Inhibition of adenylate cyclase by hormones and neurotransmitters, Mol. Cell Endocrinol. 16: 147 (1979).CrossRefGoogle Scholar
  3. 3.
    M. Rodbell, The role of hormone receptors and GTP-regulatory proteins in membrane transduction, Nature 284: 17 (1980).CrossRefGoogle Scholar
  4. 4.
    D. M. F. Cooper, W. Schlegel, M. C. Lin, and M. Rodbell, The fat cell adenylate cylase system. Characterization and manipulation of its bimodal regulation by GTP, J. Biol. Chem. 254: 8927 (1979).Google Scholar
  5. 5.
    D. M. F. Cooper, C. Londos, and M. Rodbell, Adenosine receptor-mediated inhibition of rat cerebral cortical adenylate cyclase by a GTP-dependent process, Mol. Pharmacol. 18: 598 (1980).Google Scholar
  6. 6.
    T. Trost and U. Schwabe, Adenosine receptors in fat cells:Identification by (-)-N -[3H]phenylisopropyladenosine binding, Mol. Pharmacol. 19: 228 (1981).Google Scholar
  7. 7.
    D. C. U’Prichard and S. H. Snyder, Interactions of divalent cations and guanine nucleotides at a noradrenergic receptor binding sites in bovine brain mechanisms, J. Neurochem. 34: 385 (1980).CrossRefGoogle Scholar
  8. 8.
    E. M. Ross and A. G. Gilman, Biochemical properties of hormone-sensitive adenylate cyclase, Ann. Review Biochem. 49: 533 (1980).CrossRefGoogle Scholar
  9. 9.
    K. B. Seamon and J. W. Daly, Guanosine 5’-(ß,Y-imido) triphosphate inhibition of forskolin-activated adenylate cyclase is mediated by the putative inhibitory guanine nucleotide regulatory protein, J. Biol. Chem. 257: 11591 (1981).Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Dermot M. F. Cooper
    • 1
  • Siu-Mei Helena Yeung
    • 1
  • Edward Perez-Reyes
    • 1
  • Linda H. Fossom
    • 1
  1. 1.Department of PharmacologyUniversity of Colorado School of MedicineDenverUSA

Personalised recommendations