On the Role of Glial Cells in the Mammalian Nervous System

Abstract

Abstract The synthesis, uptake, and efflux of some putative neurotransmitters by cultured rat glial tumor cells were studied. Three glial cell clones were capable of pyridoxal-dependent synthesis of γ-aminobutyrate both in cell-free homogenates and in intact cells in monolayers. Substantial catabolism of γ-aminobutyrate was not found. Synthesis of taurine and isethionic acid, but not β-alanine, by one of the glioma lines was also shown. Glioma lines were found to take up glutamate and exhibited Na+-dependent uptake of γ-aminobutyrate. The uptake of γ-aminobutyrate consisted of a slow saturable component (Kt ∼ 13 to 30 µm) and a rapid nonsaturable component. Both of these were antagonized by some structural analogs of γ-aminobutyrate as well as by taurine, β-alanine, bicuculline, and low temperature. Similar kinetic parameters were found for three different glioma lines. Fibroblast-like cells obtained from rat brain cell cultures had only the nonsaturable component of γ-aminobutyrate uptake. Taurine uptake also consisted of two Na+-dependent and temperature-dependent components: a rapid saturable component (Kt ∼ 10 to 17 µm) and a nonsaturable component which varied in magnitude between cell lines. These uptakes were antagonized by β-alanine but not by γ-aminobutyrate. The glioma lines also excreted the concentrated γ-aminobutyrate into the extracellular milieu, but could maintain cell to medium concentration ratios of g80-fold. In taurine efflux experiments, cell to medium concentration ratios in excess of 1500-fold could be maintained by one of the gliomas. The data are consistent with a possible role of central nervous system glial cells in the modulation of neuronal excitability via control of the levels of neuroactive substances in the extracellular milieu of neurons.