Organotins disrupt components of glutamate homeostasis in rat astrocyte cultures.
A rat cortical astrocyte preparation was used to investigate the effects of organotins on glutamate regulation by astrocytes. Exposure of astrocytes to low levels of organotins produced significant changes in two key components of glutamate homeostasis: glutamine synthetase (CS) activity and the high-affinity transport of L-glutamate. Trimethyltin (TMT), triethyltin (TET), and triphenyltin (TPT) exhibited differential abilities to reduce GS activity and glutamate uptake. Cultures incubated with 1 microM TET or TPT, but not TMT, exhibited a marked decrease in GS activity. Exposure to TET or TPT also produced a significant decrease in glutamate transport activity that was not observed with TMT. These declines in activity were not attributable to cell loss as measured by MTT reduction and lactate dehydrogenase (LDH) leakage. Since the loss of GS activity and transporter activity was not seen with acute organotin exposure, it is most likely attributable to a decreased presence of fully functioning protein. While the attenuation of GS and glutamate transporter activities by organotins does not match their pattern of neurotoxicity, the results indicate the potential for subtoxic concentrations of these compounds to increase extracellular glutamate and interact with other excitotoxic episodes.
Karpiak
V C
VC
Department of Pharmaceutical Sciences, School of Pharmacy and Allied Health Sciences, University of Montana, Missoula 59812, USA.
Bridges
R J
RJ
Eyer
C L
CL
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009947:Organotin Compounds / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D009947:Organotin Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D005974:Glutamate-Ammonia Ligase; C022616:thiazolyl blue