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• W2026867145 abstract "The influence of lipid peroxidation on 5-HT2 receptor binding was examined in prefrontal cortex membranes from sheep brain. Lipid peroxidation was induced with ascorbic acid and ferrous sulphate and measured by the thiobarbituric acid method. In lipid-peroxidized membranes, [3H]ketanserin specific binding was inhibited. The Bmax values decreased by 80%, from 50.1 +/- 3.5 fmol/mg protein in control membranes to 10.1 +/- 2.0 fmol/mg protein in peroxidized membranes, indicating a decrease in the number of 5-HT2 binding sites. However, the KD values for the [3H]ketanserin specific binding did not significantly change. In order to further characterize [3H]ketanserin binding, the inhibition potency (IC50 values) of antagonists or agonists of serotonin and dopamine receptors for [3H]ketanserin specific binding was determined. In control membranes, the order of inhibition potency of the drugs tested was the following: ketanserin (-log[IC50]=8.56 +/- 0.70] > ritanserin (-log [IC50]=8.13 +/- 0.30)>methysergide (-log[IC50]= 7.42 +/- 0.50)> spiperone (-log[IC50]=7.23 +/- 0.18 > serotonin (-log [IC50] = 6.99 +/- 0.65)> haloperidol (-log[IC50]= 6.95 +/- 0.65) > dopamine (-log [IC50] = 5.82 +/- 0.76). After membrane lipid peroxidation, the IC50 value for ritanserin was significantly increased, suggesting a decreased capacity for displacing [3H]ketanserin specific binding. Other antagonists of 5-HT2 receptors showed apparent increases in IC50 values upon peroxidation, whereas spiperone was shown to be the most potent drug (-log[IC50]= 7.19 +/- 1.06) in inhibiting [3H]ketanserin specific binding. A decrease in polyunsaturated fatty acids, namely docosahexaenoic acid (22:6) was also observed in peroxidized membranes. These results indicate a modulating role of the surrounding lipids and of the physical properties of the membranes on the binding activity of 5-HT2 receptors upon the lipid peroxidation process, which can be involved in the tissue impairment that occurs during the aging process and in post-ischemic situations." @default.
• W2026867145 created "2016-06-24" @default.
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• W2026867145 date "1995-12-01" @default.
• W2026867145 modified "2023-10-16" @default.
• W2026867145 title "Influence of lipid peroxidation on [3H]ketanserin binding to 5-HT2 prefrontal cortex receptors" @default.
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• W2026867145 doi "https://doi.org/10.1016/0197-0186(95)00045-a" @default.
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