Allosteric modulation of A(2A) adenosine receptors by amiloride analogues and sodium ions

Biochem Pharmacol. 2000 Sep 1;60(5):669-76. doi: 10.1016/s0006-2952(00)00360-9.


Allosteric regulation of rat A(2A) adenosine receptors by amiloride, amiloride analogues, and sodium ions was studied by investigating their ability to influence the dissociation of [(3)H]4-2-[7-amino-2-(2-furyl)-1,2,4-triazolo[1,5-a][1,3, 5]triazin-5-yl-amino]ethylphenol ([(3)H]ZM241385) from receptors in rat striatal membranes. Both amiloride and its analogues accelerated the dissociation, the analogues being more potent than amiloride itself. In contrast, sodium ions decreased the rate of [(3)H]ZM241385 dissociation in a concentration-dependent manner, and this rate was not influenced by guanosine triphosphate, N-ethylmaleimide, suramin, or the selective A(2A) adenosine receptor antagonist, 5-amino-2-(2-furyl)-7(2-phenylethyl)pyrazolo[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine (SCH58261). The effect of competition between the amiloride analogue 5-(N,N-hexamethylene)amiloride (HMA) and sodium ions on [(3)H]ZM241385 dissociation was also explored. The addition of sodium ions resulted in a concentration-dependent rightward shift of the HMA response curve. The slopes of the HMA concentration-response curves in the presence and absence of sodium ions were not significantly different, which suggests that sodium ions and amiloride analogues act at a common allosteric site on the A(2A) adenosine receptor. There was a lack of correlation between the displacement of ligand binding and the allosteric potencies of the amiloride analogues.

MeSH terms

  • Allosteric Regulation
  • Amiloride / analogs & derivatives*
  • Amiloride / pharmacology*
  • Animals
  • Binding, Competitive
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Diuretics / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • In Vitro Techniques
  • Purinergic P1 Receptor Antagonists
  • Radiopharmaceuticals / metabolism
  • Rats
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1 / metabolism*
  • Sodium / pharmacology*
  • Sodium Chloride / pharmacology
  • Time Factors
  • Triazines / metabolism
  • Triazoles / metabolism
  • Tritium


  • Diuretics
  • Purinergic P1 Receptor Antagonists
  • Radiopharmaceuticals
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1
  • Triazines
  • Triazoles
  • ZM 241385
  • Tritium
  • 5-(N,N-hexamethylene)amiloride
  • Sodium Chloride
  • Amiloride
  • Sodium