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Ascorbic Acid Inhibits 125 I‐SCH 23982 Binding but Increases the Affinity of Dopamine for D 1 Dopamine Receptors
Author(s) -
Kimura Kazuhiro,
Sidhu Anita
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63062093.x
Subject(s) - dopamine , ascorbic acid , chemistry , dopaminergic , binding site , receptor , dopamine receptor , agonist , lipid peroxidation , biochemistry , medicine , endocrinology , biology , antioxidant , food science
Effects of ascorbic acid (AA) on 125 I‐SCH 23982 binding to D 1 dopaminergic receptors in membrane preparations from rat striatum were investigated. AA in the range of 0.03 µ M –0.33 m M inhibited 75% of specific binding of 125 I‐SCH 23982 in a dose‐dependent manner. At higher concentrations, this inhibition of binding activity by AA was less potent, and 3.3 m M AA inhibited only 30% of specific binding. Reduced glutathione did not alter the inhibition of binding by 0.33 m M AA, but reduced the inhibition by 3.3 m M AA to 8% of specific binding. The loss of specific binding by AA was rescued by 1 m M EDTA, an inhibitor of lipid peroxidation. In the absence of AA, competition experiments with the agonist, dopamine, revealed the presence of high‐affinity ( K h = 224.9 ± 48.9 n M ) and low‐affinity ( K l = 21,100 ± 2,400 n M ) binding sites. Although the maximum binding of 125 I‐SCH 23982 decreased to 40% without affecting the K D value in the presence of 1.67 m M AA, the value of the high‐affinity site for dopamine was increased ( K h = 23.3 ± 9.4 n M ) and that of the low‐affinity site was decreased ( K l = 136,800 ± 40,900 n M ). These results suggest that AA may affect D 1 dopamine receptor function by lipid peroxidation, competition with dopamine for low‐affinity sites, and reduced oxidation of dopamine.