GTP differentially affects antagonist radioligand binding to adenosine A(1) and A(2A) receptors in human brain

Neuropharmacology. 2000 Sep;39(12):2374-80. doi: 10.1016/s0028-3908(00)00081-2.


The effect of guanosine triphosphate (GTP) on the interaction of antagonists with human adenosine A(1) and A(2A) receptors was studied using whole-hemisphere sections from human brain and membranes from Chinese hamster ovary (CHO) cells expressing human A(1) and A(2A) receptors. Adenosine A(1) receptors, studied using [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX) as radioligand, showed the expected regional distribution in human brain. Addition of 500 microM GTP significantly increased (23-55%) [3H]DPCPX binding in all regions measured. In CHO cells transfected with human adenosine A(1) receptor cDNA, the number of receptors, B(max), increased from 401 (359-442) to 667 (592-743) fmol/mg protein upon addition of GTP. [3H]5-Amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo-[4,3-e]-1,2, 4-triazolo-[1,5-c]-pyrimidine ([3H]SCH 58261), a selective adenosine A(2A) receptor ligand, showed saturable binding to membranes from CHO cells transfected with adenosine A(2A) receptor cDNA and was localized to striatum and globus pallidus in human brain sections. Addition of GTP did not significantly change [3H]SCH 58261 binding to brain sections or CHO cell membranes. These results indicate that human A(1) and A(2A) receptors are not substantially different from those of the rat as regards regulation by GTP and interactions with endogenous adenosine in binding experiments. However, the relative abundance of the receptors differs between species, and this may be related to the differences observed in the potency of the endogenous agonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Brain Chemistry / drug effects*
  • CHO Cells
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cricetinae
  • Guanosine Triphosphate / pharmacology*
  • Humans
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines
  • Radioligand Assay
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1 / drug effects*
  • Thermodynamics
  • Triazoles
  • Xanthines


  • 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1
  • Triazoles
  • Xanthines
  • Guanosine Triphosphate
  • 1,3-dipropyl-8-cyclopentylxanthine