Ascorbic acid inhibits 125I-SCH 23982 binding but increases the affinity of dopamine for D1 dopamine receptors.
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 microM-0.33 mM 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 mM AA inhibited only 30% of specific binding. Reduced glutathione did not alter the inhibition of binding by 0.33 mM AA, but reduced the inhibition by 3.3 mM AA to 8% of specific binding. The loss of specific binding by AA was rescued by 1 mM EDTA, an inhibitor of lipid peroxidation. In the absence of AA, competition experiments with the agonist, dopamine, revealed the presence of high-affinity (Kh = 224.9 +/- 48.9 nm) and low-affinity (Kl = 21,100 +/- 2,400 nM) binding sites. Although the maximum binding of 125I-SCH 23982 decreased to 40% without affecting the KD value in the presence of 1.67 mM AA, the value of the high-affinity site for dopamine was increased (Kh = 23.3 +/- 9.4 nM) and that of the low-affinity site was decreased (Kl = 136,800 +/- 40,900 nM). 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.
Department of Pediatrics, Georgetown University Children's Medical Center, Georgetown University, Washington, D.C.
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Kimura
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Sidhu
D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001552:Benzazepines / Q000031:analogs & derivatives* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D007457:Iodine Radioisotopes; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*
C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D001552:Benzazepines; D007457:Iodine Radioisotopes; D017447:Receptors, Dopamine D1; D004492:Edetic Acid; D005978:Glutathione; D001205:Ascorbic Acid; D004298:Dopamine