Due to ethanol's low potency and low level of toxicity, high amounts of ethanol are consumed to achieve pharmacological effects. Blood levels of ethanol in chronic alcoholics may reach as high as 80-100 mM. We undertook a series of studies to determine if these high levels of ethanol stimulated osmoregulatory processes in cultured astrocytes. The uptake and efflux of taurine, the major osmoregulatory amino acid with potentially neuroprotective actions, was assessed. In addition, uptake and efflux of the excitatory amino acid aspartate was studied since astrocytes are vital in maintaining proper synaptic excitatory amino levels through uptake, metabolism, and efflux. Ethanol exposure for 96 h resulted in increased uptake of both 3H-taurine and 3H-D-asparate. There were no significant changes in transporter function at 24 h consistent with the delayed time course of transporter up-regulation seen during chronic hyperosmotic stress. Following EtOH withdrawal, efflux of preloaded 3H-taurine was significantly increased as compared to controls for up to 1 h. In contrast to the efflux profile seen during hypotonic induced swelling and regulatory volume decrease (RVD), no increased 3H-D-asparate efflux was demonstrated. Cell volume measurements suggest that inhibition of the normal RVD response be involved in the increased taurine release.
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