Elsevier

Neurotoxicology and Teratology

Volume 16, Issue 3, May–June 1994, Pages 277-281
Neurotoxicology and Teratology

Article
Differences in the reserpine-sensitive storage in vivo of 1-methyl-4-phenylpyridinium in rats and mice may explain differences in catecholamine toxicity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

https://doi.org/10.1016/0892-0362(94)90049-3Get rights and content

Abstract

Administration of reserpine, an inhibitor of vesicular catecholamine storage, differentially reduced the accumulation of MPP+ formed from MPTP in rats and mice. The effects were most pronounced in the adrenal gland for either species. In rats, reserpine decreased striatal and hippocampal MPP+ levels while in mice reserpine did not affect the disposition of MPP+ in the striatum but decreased hippocampal MPP+. The data suggest that mice may be more sensitive to the toxicant because less striatal MPP+ appears to be stored in the reserpine-sensitive storage vesicle.

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      Brain samples (0.3–1 mg protein) were sonicated in 200 μl 0.1 M perchloric acid containing 0.4 mM sodium metabisulfite and 0.1 mM EDTA disodium dihydrate (Naoi et al., 1987), and following centrifugation, a 50 μl aliquot was separated by HPLC. The HPLC system was adapted from previous methods (Naoi, et al., 1987; Russo, et al., 1994) and comprised a 4.6 mm × 250 mm Cosmosil 5 C18-MS-II column (Nacalai USA Inc., San Diego, CA), using a pH 7.75 mobile phase (20 mM boric acid, 3 mM tetrabutylammonium sulfate, 0.25 mM hexane sulfonic acid and 7.5% isopropanol) pumped at 0.8 ml/min (Shimadzu LC-10ADVP, Columbia, MD) with native fluorescence detection of MPP+ achieved at excitation/emission wavelengths of 295 and 375 nm (Shimadzu RF-10AXL). Less tailing of the MPP+ peak was obtained with this column compared to other tested reverse-phase columns.

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