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Clopidogrel active metabolite sigma -1 antagonist, propranolol, ibuprofen, and dipyridamole). We also studied the distribution of sigma-1 receptors at different tissues, i.e., skeletal muscle, heart, cerebral cortex, thymus, pancreas, skin, liver, kidney, and bone. At all sites investigated, sigma-1 receptor densities were present only in muscle, liver, thymus, pancreas, and skin. In other organs sigma-1 receptor concentration was similar to that of dopamine D1 receptor. In cerebral cortex, sigma-1 receptor concentrations differed significantly between healthy subjects of both sexes. In male subjects, sigma-1 receptor densities were found only in skin (n = 38) and in kidney (n = 31) (and the total concentrations were not statistically different). In female subjects the sigma-1 receptor densities in cerebral cortex remained unchanged. It must be mentioned that there are no reliable sex differences in the concentrations of sigma-1 receptors in skin, heart, and pancreas. The expression of α-synuclein was evaluated by Western blotting analysis of plasma protein extracts brain, adrenal glands, skeletal muscle, and retina. The results confirmed presence of α-synuclein in all tissues examined. expression was significantly greater in the brains of brain- or adrenal-depleted animals (Fig. 5). Furthermore, plasma protein extracts from the brain, adrenal glands, and muscle contained significantly higher levels of α-synuclein if protein extracts from the liver were also measured. These results demonstrate that sigma-1 receptor blockade effectively decreases the expression and inducibility of α-synuclein in tissues that are crucial for the normal and pathological functions of the brain. FIGURE 5 View largeDownload slide Male and female brain α-synuclein (a) protein (b) extracts, and (c) percentage of α-synuclein in the brain, adrenal gland, and muscle. Values are means ± what is drug clopidogrel SEM. Ratio was determined from two groups of eight mice each. Dashed line: control; blue sigma-1 antagonists; black line: inverse antagonists. In all groups of eight mice, values were not significantly different (P = 0.21, P 0.34, and 0.65, respectively). FIGURE 5 View largeDownload slide Male and female brain α-synuclein (a) protein (b) extracts, and (c) percentage of α-synuclein in the brain, adrenal gland, and muscle. Values are means ± SEM. Ratio was determined from two groups of eight mice each. Dashed line: control; blue sigma-1 antagonists; black line: inverse antagonists. In all groups of eight mice, values were not significantly different (P = 0.21, P 0.34, and 0.65, respectively). In the retina, sigma-1 receptors were present, but their expression was significantly reduced in sigma-1 receptor-deficient animals (n = 24). Furthermore, these animals had significantly less total cone number (n = 19), compared with sigma-1 control animals, and.
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