Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures: altered uptake and efflux of rubidium, l-glutamate and D-aspartate
Michael Aschner, M. Gannon, H. K. Kimelberg
Studies were undertaken to assess the effects of trimethyl tin (TMT) on metabolic functions in primary neonatal rat cultured astrocytes. Concentrations as low as 10-5 M TMT significantly inhibited the initial rate (1 min) of uptake of 86RbCl, used as a tracer for K+. TMT also markedly inhibited the initial rate (1 min) of Na+-dependent uptake of l-[3H]glutamate and d-[3H]aspartate, and stimulated the release of intracellular 86Rb+, -[3H]glutamate and d[3H]aspartate in a dose-dependent fashion. These observations support the hypothesis that the astrocyte plasma membrane is potentially an important target for TMT's toxic effect and specifically that small concentrations of this organometal can inhibit the ability of astrocytes to maintain a transmembrane K+ gradient. This would be expected to compromise the ability of astrocytes to control extracellular K+ either by spatial buffering or active uptake, and exacerbate on-going swelling. Increased levels of glutamate and aspartate in the extracellular fluid upon release from astrocytes may play an important role in TMT neurotoxicity.
Extracellular Fluid
Astrocyte
d-Aspartate
l-Glutamate
Trimethyl tin
Aschner, M., Gannon, M., & Kimelberg, H. K. (1992). Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures: altered uptake and efflux of rubidium, l-glutamate and D-aspartate. Brain Research, 582(2), 181-185. https://doi.org/10.1016/0006-8993(92)90131-R
Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures : altered uptake and efflux of rubidium, l-glutamate and D-aspartate. / Aschner, Michael; Gannon, M.; Kimelberg, H. K.
In: Brain Research, Vol. 582, No. 2, 12.06.1992, p. 181-185.
Aschner, M, Gannon, M & Kimelberg, HK 1992, 'Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures: altered uptake and efflux of rubidium, l-glutamate and D-aspartate', Brain Research, vol. 582, no. 2, pp. 181-185. https://doi.org/10.1016/0006-8993(92)90131-R
Aschner M, Gannon M, Kimelberg HK. Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures: altered uptake and efflux of rubidium, l-glutamate and D-aspartate. Brain Research. 1992 Jun 12;582(2):181-185. https://doi.org/10.1016/0006-8993(92)90131-R
Aschner, Michael ; Gannon, M. ; Kimelberg, H. K. / Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures : altered uptake and efflux of rubidium, l-glutamate and D-aspartate. In: Brain Research. 1992 ; Vol. 582, No. 2. pp. 181-185.
@article{181d893d3bc348e491949dc1fe0d29cf,
title = "Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures: altered uptake and efflux of rubidium, l-glutamate and D-aspartate",
abstract = "Studies were undertaken to assess the effects of trimethyl tin (TMT) on metabolic functions in primary neonatal rat cultured astrocytes. Concentrations as low as 10-5 M TMT significantly inhibited the initial rate (1 min) of uptake of 86RbCl, used as a tracer for K+. TMT also markedly inhibited the initial rate (1 min) of Na+-dependent uptake of l-[3H]glutamate and d-[3H]aspartate, and stimulated the release of intracellular 86Rb+, -[3H]glutamate and d[3H]aspartate in a dose-dependent fashion. These observations support the hypothesis that the astrocyte plasma membrane is potentially an important target for TMT's toxic effect and specifically that small concentrations of this organometal can inhibit the ability of astrocytes to maintain a transmembrane K+ gradient. This would be expected to compromise the ability of astrocytes to control extracellular K+ either by spatial buffering or active uptake, and exacerbate on-going swelling. Increased levels of glutamate and aspartate in the extracellular fluid upon release from astrocytes may play an important role in TMT neurotoxicity.",
keywords = "Astrocyte, d-Aspartate, l-Glutamate, Rat, Rubidium, Transport, Trimethyl tin",
author = "Michael Aschner and M. Gannon and Kimelberg, {H. K.}",
journal = "Brain Research",
T1 - Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures
T2 - altered uptake and efflux of rubidium, l-glutamate and D-aspartate
AU - Aschner, Michael
AU - Gannon, M.
AU - Kimelberg, H. K.
N2 - Studies were undertaken to assess the effects of trimethyl tin (TMT) on metabolic functions in primary neonatal rat cultured astrocytes. Concentrations as low as 10-5 M TMT significantly inhibited the initial rate (1 min) of uptake of 86RbCl, used as a tracer for K+. TMT also markedly inhibited the initial rate (1 min) of Na+-dependent uptake of l-[3H]glutamate and d-[3H]aspartate, and stimulated the release of intracellular 86Rb+, -[3H]glutamate and d[3H]aspartate in a dose-dependent fashion. These observations support the hypothesis that the astrocyte plasma membrane is potentially an important target for TMT's toxic effect and specifically that small concentrations of this organometal can inhibit the ability of astrocytes to maintain a transmembrane K+ gradient. This would be expected to compromise the ability of astrocytes to control extracellular K+ either by spatial buffering or active uptake, and exacerbate on-going swelling. Increased levels of glutamate and aspartate in the extracellular fluid upon release from astrocytes may play an important role in TMT neurotoxicity.
AB - Studies were undertaken to assess the effects of trimethyl tin (TMT) on metabolic functions in primary neonatal rat cultured astrocytes. Concentrations as low as 10-5 M TMT significantly inhibited the initial rate (1 min) of uptake of 86RbCl, used as a tracer for K+. TMT also markedly inhibited the initial rate (1 min) of Na+-dependent uptake of l-[3H]glutamate and d-[3H]aspartate, and stimulated the release of intracellular 86Rb+, -[3H]glutamate and d[3H]aspartate in a dose-dependent fashion. These observations support the hypothesis that the astrocyte plasma membrane is potentially an important target for TMT's toxic effect and specifically that small concentrations of this organometal can inhibit the ability of astrocytes to maintain a transmembrane K+ gradient. This would be expected to compromise the ability of astrocytes to control extracellular K+ either by spatial buffering or active uptake, and exacerbate on-going swelling. Increased levels of glutamate and aspartate in the extracellular fluid upon release from astrocytes may play an important role in TMT neurotoxicity.
KW - Astrocyte
KW - d-Aspartate
KW - l-Glutamate
KW - Rat
KW - Rubidium
KW - Transport
KW - Trimethyl tin
JO - Brain Research
JF - Brain Research