B. Kull et al., GTP differentially affects antagonist radioligand binding to adenosine A(1) and A(2A) receptors in human brain, NEUROPHARM, 39(12), 2000, pp. 2374-2380
The effect of guanosine triphosphate (GTP) on the interaction of antagonist
s with human adenosine A(1) and A(2A) receptors was studied using whole-hem
isphere sections from human brain and membranes from Chinese hamster ovary
(CHO) cells expressing human A(1) and A(2A) receptors. Adenosine A(1) recep
tors, studied using [H-3]1,3-dipropyl-8-cyclopentylxanthine ([H-3]DPCPX) as
radioligand, showed the expected regional distribution in human brain. Add
ition of 500 mu M GTP significantly increased (23-55%) [H-3] 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. [H-3]5-Amino-7-(2-
phenylethyl)-2-(2-furyl)pyrazolo- [4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidin
e ([H-3]SCH 58261), a selective adenosine A(2A) receptor ligand, showed sat
urable binding to membranes from CHO cells transfected with adenosine A(2A)
receptor cDNA and was localized to striatum and globus pallidus in human b
rain sections. Addition of GTP did not significantly change [H-3]SCH 58261
binding to brain sections or CHO cell membranes. These results indicate tha
t 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 a
denosine in binding experiments. However, the relative abundance of the rec
eptors differs between species, and this may be related to the differences
observed in the potency of the endogenous agonist. (C) 2000 Elsevier Scienc
e Ltd. All rights reserved.