Taurine inhibits the phosphorylation of two endogenous proteins (M(r) ? 140 and ?20 K) in subcellular preparations of rat cortex.

The effects of exogenous taurine on the phosphorylation of proteins in hypo-osmotically shocked synaptosomes (P(2) fraction) prepared from rat cortex were investigated. Taurine (2-20 mM) inhibited the phosphorylation of two bands of protein with molecular weights of ? 140 and ? 20 K in a concentration related manner as shown by one-dimensional SDS-PAGE. Kinetic studies using 10 mM tauring demonstrated that the inhibitory effect occurred at approx. 1 min after the start of the reaction. Phosphatase activity was also seen in these kinetic studies. Endogenous taurine levels in the tissue preparation utilized in the reaction system were determined to be 0.12 mM. Further separation of the proteins with high-resolution two-dimensional SDS-PAGE indicated that the ? 140 K molecular weight protein had an isoelectric point of 6.1 and its phosphorylation was inhibited 88% by 10 mM taurine; the ? 20 K molecular weight protein had an isoelectric point of 5.6 and its phosphorylation was inhibited 72% by 10 mM taurine. The taurine analogue and taurine transport inhibitor, guanidinoethanesulfonic acid (GES), inhibited the phosphorylation of the ? 140 K molecular weight protein but did not have any effect on the ? 20 K molecular weight protein. The phosphorylation of the ? 20 K molecular weight protein was inhibited 55% by glycine but was not affected by either ?-alanine or GABA. These results point out the relative specificity of the taurine effect on the low molecular weight protein. Subcellular fractionation demonstrated that the ? 20 K molecular weight phosphoprotein was enriched in the cytosol. These studies suggest that taurine which has been implicated to be a neuromodulator may influence neuroactivity by inhibiting protein phosphorylation.