Organotins disrupt components of glutamate homeostasis in rat astrocyte cultures

Arat 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 component s of glutamate homeostasis: glutamine synthetase (GS) activity and the high -affinity transport of L-glutamate. Trimethyltin (TMT), triethyltin (TET), and triphenyltin (TPT) exhibited differential abilities to reduce GS activi ty and glutamate uptake. Cultures incubated with 1 muM TET or TPT, but not TMT, exhibited a marked decrease in GS activity. Exposure to TET or TPT als o 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) leak age. Since the loss of GS activity and transporter activity was not seen wi th acute organotin exposure, it is most likely attributable to a decreased presence of fully functioning protein. While the attenuation of GS and glut amate transporter activities by organotins does not match their pattern of neurotoxicity, the results indicate the potential for subtoxic concentratio ns of these compounds to increase extracellular glutamate and interact with other excitotoxic episodes.