ASCORBATE/FE3(+)-INDUCED PEROXIDATION AND INHIBITION OF THE BINDING OF A(1) ADENOSINE RECEPTOR LIGANDS IN RAT-BRAIN MEMBRANES

被引:8
作者
OLIVEIRA, JC [1 ]
CONSTANTINO, MD [1 ]
SEBASTIAO, AM [1 ]
RIBEIRO, JA [1 ]
机构
[1] GULBENKIAN INST SCI,PHARMACOL LAB,P-2781 OEIRAS,PORTUGAL
关键词
D O I
10.1016/0197-0186(94)00124-D
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effect of peroxidation induced by the ascorbate/Fe3+ system on the binding properties of the A(1) adenosine receptor, was studied in rat brain membranes, using the agonist, [H-3]R-N-6-phenylisopropyladenosine ([H-3]R-PIA), and the antagonist, [H-3]1,3 -dipropyl-8-cyclopentylxanthine ([H-3]DPCPX). For the agonist, as well as for the antagonist, the number of binding sites (B-max) was significantly (P < 0.05) reduced after pretreatment of the membranes with ascorbate/Fe3+. The affinity of the agonist for the binding sites was not statistically modified (P > 0.05) after ascorbate/Fe3+ pretreatment, whereas the K-d value of the antagonist was increased (P < 0.05) by a factor of 2. Ascorbate/Fe3+ pretreatment affected agonist binding in the presence of GTP in a similar way as that observed in the absence of GTP, suggesting that peroxidation also affects agonist binding to A(1) adenosine receptors uncoupled to G-proteins. The results suggest that when brain membranes suffer free radical oxidative damage, the adenosine modulation of neuronal activity through A(1) receptors could be less efficient.
引用
收藏
页码:263 / 268
页数:6
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