Induction of metallothionein-I (MT-I) mRNA in primary astrocyte cultures is mediated by hypotonicity and not ethanol (EtOH) per se

Metallothionein (MT) mRNA was determined in rat astrocyte cultures in response to ethanol (EtOH). MT-I mRNA was significantly increased after 6 h exposure to isosmotic EtOH, but not hyperosmotic EtOH. Exposure to a hyposmotic/hypotonic solution also led to a significant increase in the expression of astrocytic MT-I mRNA. The large increase in MT-I mRNA was not due to removal of extracellular NaCl, because this effect was reversed by replacement of NaCl with N-methyl D-glucamine chloride. A significant decrease in MT-I mRNA was also noted in astrocytes exposed to an EtOH-free hyperosmotic/hypertonic solution. These results suggest (1) that EtOH per se does not directly induce MT-I mRNA expression, (2) that the induction by EtOH of MT-I mRNA is secondary to hypotonicity, and (3) that hyperosmotic/hypertonic exposure is associated with reduced expression of MT-I mRNA in astrocyte cultures.