Magnesium ion exerts a central role in the regulation of inhibitory adenosine receptors

S. M.H. Yeung, L. H. Fossom, Donald Gill, D. M.F. Cooper

Research output: Contribution to journalArticle

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Abstract

Guanine nucleotides and Mg2+ differentially regulate agonist binding to adenosine (R(i)) receptors in fat-cell plasma membranes. GTP alone decreases binding of the agonist ligand [3H]N6-cyclohexyladenosine (CHA) by increasing the dissociation constant (K(d)). Mg2+ alone also decreases [3H]CHA binding, which is associated with a decrease in the number of receptors and in the dissociation constant. In the presence of Mg2+, the effect of GTP is to increase [3H]CHA binding by increasing the total number of receptors. It thus appears that Mg2+ acts specifically at a bivalent-cation site which, with GTP, regulates agonist binding. This putative Mg site is highly sensitive to alkylating agents. Mild treatment with N-ethylmaleimide (NEM) abolishes the characteristic GTP effect on agonist binding in the presence of Mg2+. In addition, the effect of Mg2+ alone is also eliminated. The effect of GTP alone is largely unaltered. Studies of the adenylate cyclase activity indicate that this NEM treatment also abolishes the inhibition of basal activity by adenosine analogues, whereas guanylyl imidodiphosphate inhibition of forskolin-stimulated activity is only slightly impaired at this NEM concentration. These observations indicate that a Mg2+ 'site' or 'component' is required for the integration of receptor (R(i)) occupancy with regulation of catalytic activity (C). The regulatory role of Mg2+ is more demonstrable in receptor-GTP-regulatory-protein (R(i)-N(i)) interactions than in GTP-regulatory-protein-catalytic-unit (N(i)-C) interactions.

Original languageEnglish (US)
Pages (from-to)91-100
Number of pages10
JournalBiochemical Journal
Volume229
Issue number1
DOIs
StatePublished - Jan 1 1985

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Purinergic P1 Receptors
Guanosine Triphosphate
Magnesium
Ethylmaleimide
Ions
Cell membranes
GTP-Binding Proteins
Adenosine
Cell Membrane
Guanylyl Imidodiphosphate
Guanine Nucleotides
Alkylating Agents
Colforsin
Adenylyl Cyclases
Adipocytes
Cations
Catalyst activity
Fats
Ligands

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yeung, S. M.H. ; Fossom, L. H. ; Gill, Donald ; Cooper, D. M.F. / Magnesium ion exerts a central role in the regulation of inhibitory adenosine receptors. In: Biochemical Journal. 1985 ; Vol. 229, No. 1. pp. 91-100.
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Magnesium ion exerts a central role in the regulation of inhibitory adenosine receptors. / Yeung, S. M.H.; Fossom, L. H.; Gill, Donald; Cooper, D. M.F.

In: Biochemical Journal, Vol. 229, No. 1, 01.01.1985, p. 91-100.

Research output: Contribution to journalArticle

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