Alkyltin inhibition of ATPase activities in tissue homogenates and subcellular fractions from adult and neonatal rats

Abstract

Inhibition of ATPase activities by triethyltin (TET), diethyltin (DET), monoethyltin (MET), and trimethyltin (TMT) was studied in homogenates of brain and liver from adult and neonatal rats. In the adult, sensitivities were as follows: mitochondrial ATPase of liver ⪢ Na +,K +-ATPase of brain ⋍ mitochondrial ATPase of brain > nonspecific ATPase of brain and liver. MET did not produce significant inhibition. ATPase activities in brain and liver homogenates from TET-treated adult rats did not differ from controls. Mitochondrial ATPase in brain homogenates from 5-day-old rats was two orders of magnitude more sensitive to TET than brain homogenates from adult rats (IC 50 of 2.5 μ m in the 5-day-old neonate vs 260 μ m in the adult). By contrast, isolated mitochondria and synaptosomal fractions from adult and neonatal brains were equally sensitive to TET (IC 50 = 1–3 μ m). At 10 days of age, following the onset of myelination, the IC 50 for TET inhibition of brain mitochondrial ATPase increased to 71 μ m. Myelin added directly to isolated mitochondria also reduced TET-induced inhibition. It is concluded that in vivo brain tin concentrations in 5-day-old rats following a neurotoxic dose of TET are sufficient to inhibit brain mitochondrial ATPase, whereas in adults, tin concentrations are insufficient for inhibition. In the adult rat, TET binding to myelin appears to prevent inhibition of brain mitochondrial ATPase, and the target of toxic action may be myelin. In the neonateal rat, TET may inhibit oxidative phosphorylation in unmyelinated brain tissue, leading to neuronal cell death.