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ORGANIC MERCURIAL ENCEPHALOPATHY: IN VIVO AND IN VITRO EFFECTS OF METHYL MERCURY ON SYNAPTOSOMAL RESPIRATION
Author(s) -
Verity M. A.,
Brown W. Jann,
Cheung M.
Publication year - 1975
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1975.tb04405.x
Subject(s) - respiration , chemistry , stimulation , dinitrophenol , biochemistry , neurotoxicity , glutamate receptor , oxidative phosphorylation , synaptosome , endocrinology , toxicity , in vitro , biology , botany , receptor , organic chemistry
—A reproducible model of subacute methyl mercury (MeHg) intoxication was developed in the adult rat following the daily intragastric administration of 10 mg methyl mercury/kg body wt. Synaptosomes isolated from animals during the latent phase of mercury neurotoxicity (6‐10 days) demonstrated no significant change in respiratory control, State 3, State 4, or 2,4‐dinitrophenol stimulated respiration with succinate, glutamate or pyruvate plus malate. During the neurotoxic phase, a significant decline in respiratory control was evident with all substrates. Cerebellar synaptosomes revealed qualitatively similar but quantitatively greater inhibition of 2,4‐dinitrophenol stimulated respiration during the latent and neurotoxic phases with glutamate. In vitro studies of synaptosome respiration, oxidative phosphorylation and respiratory control with 5‐15 μ m ‐methyl mercury revealed a stimulation of initial State 4 respiration, loss of RCI, inhibition of State 3 but no change in the gramicidin or 2,4‐dinitrophenol uncoupled rate supported by pyruvate‐malate. Phosphate did not relieve the State 3 inhibition. At 25 μ m ‐methyl mercury and above, considerable inhibition of electron transfer occurred. At this concentration, cytochrome c oxidase was inhibited 50%. Isosmotic replacement of medium KC1 by mannitol reduced the MeHg stimulation of State 4 respiration but had no effect on MeHg inhibition of ADP stimulated respiration. Half‐maximal stimulation of State 4 respiration by MeHg occurred at [K] + ⋍ 6 m m . These findings are compatible with an energy‐linked methyl mercury induced cation translocation across the synaptosome (mitochondrial) membrane.