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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)181-185
Number of pages5
JournalBrain Research
Volume582
Issue number2
DOIs
StatePublished - Jun 12 1992
Externally publishedYes

Fingerprint

Rubidium
D-Aspartic Acid
Tin
Astrocytes
Glutamic Acid
Aspartic Acid
Poisons
Extracellular Fluid
Cell Membrane

Keywords

  • Astrocyte
  • d-Aspartate
  • l-Glutamate
  • Rat
  • Rubidium
  • Transport
  • Trimethyl tin

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

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.

Research output: Contribution to journalArticle

@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.}",
year = "1992",
month = "6",
day = "12",
doi = "10.1016/0006-8993(92)90131-R",
language = "English (US)",
volume = "582",
pages = "181--185",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

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.

PY - 1992/6/12

Y1 - 1992/6/12

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

UR - http://www.scopus.com/inward/record.url?scp=0026773025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026773025&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(92)90131-R

DO - 10.1016/0006-8993(92)90131-R

M3 - Article

VL - 582

SP - 181

EP - 185

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -