Ascorbic Acid Inhibits 125I-SCH 23982 Binding but Increases the Affinity of Dopamine for D1 Dopamine Receptors |
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Authors: | Kazuhiro Kimura Anita Sidhu |
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Institution: | Department of Pediatrics, Georgetown University Children's Medical Center, Georgetown University, Washington, D.C., U.S.A. |
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Abstract: | Abstract: Effects of ascorbic acid (AA) on 125I-SCH 23982 binding to D1 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 125I-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 125I-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 D1 dopamine receptor function by lipid peroxidation, competition with dopamine for low-affinity sites, and reduced oxidation of dopamine. |
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Keywords: | D1 dopamine receptor Dopamine Ascorbic acid Lipid peroxidation Rat striatum Radioligand binding |
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