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ALKYTIN INHIBITION OF ATPASE ACTIVITIES IN TISSUE HOMOGENATES AND SUBCELLULAR FRACTIONS FROM NEONATAL AND ADULT RATS
Citation:
Stine, K., L.W. Reiter, AND J. Masters. ALKYTIN INHIBITION OF ATPASE ACTIVITIES IN TISSUE HOMOGENATES AND SUBCELLULAR FRACTIONS FROM NEONATAL AND ADULT RATS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-88/571.
Description:
The effects of triethyltin (TET) on ATPase activities in brain and liver homogenates and subcellular fractions were compared in neonatal and adult rats. n 5 day old rats, relative sensitivities to TET inhibition were: brain and liver mitochondrial ATPase >> rain Na+/K+ ATPase > brain and liver nonspecific ATPase. itochondrial ATPase in rain homogenates from 5-day old rats was 2 orders of magnitude more sensitive to TET an brain homogenates from adult rats (IC50 of 2.5 uM in the 5 day old neonate vs. 50 of 260 uM in the adult). y contrast, isolated mitochondria and synaptosomal actions from adult and neonatal brains were equally sensitive to TET (IC50 = 1-3 uM). he other ATPase activities in both brain and liver homogenates were nearly equally sensitive to TET in the neonate as compared to the adult. t 10 days of age, following the onset of myelination, the IC50 for TET inhibition of brain mitochondrial ATPase increased to 71 uM. yelin added directly to isolated mitochondria also reduced TET-indocued inhibition. ased on previous experiments, in vivo tin concentrations in 5 day old rats following a neurotoxic dose of ET were sufficient to inhibit brain mitochondrial ATPase, whereas in adults, tin concentrations were insufficient for ATPase inhibition. n adult brains, TET binding appears to prevent in vivo inhibition of mitochondrial ATPase, and the target of toxic action may be myelin. n unmyelinated neonatal brains, TET may inhibit oxidative phosphorylation leading to neuronal cell death.