Taurine: an inhibitor of protein phosphorylation in the rat cerebral cortex
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Taurine, 2-aminoethanesulfonic acid, is an important free amino sulfonic acid occurring in the mammalian brain. It has inhibitory effects on neuroactivity and is anticonvulsive in both animal models with induced seizures and human epileptic patients. However, there has not been a defined mechanism explaining the biological role of taurine. Taurine inhibits protein phosphorylation in a hypoosmotically shocked synaptosomal preparations from rat cortex in a concentration-dependent fashion. At 10 mM, a physiologic concentration, taurine specifically inhibits the phosphorylation of a ~140K and a ~20K M, protein while 20 mM taurine has a general inhibitory effect on many proteins. Kinetic studies have demonstrated that the inhibition occurs at approximately 1 min after the reaction is initiated. The inhibition of the ~20K M^ protein shows strict structural requirements for the taurine molecule while the inhibition of the --140K M^ protein does not. Subcellular fractionation studies have demonstrated that the ~20K M^ protein is phosphorylated primarily in the isolated intrasynaptosomal cytosol. The phosphorylation of the ~20K M^ protein is Ca**-dependent and is stimulated by phorbol ester (PMA), a protein kinase C (PKC) activator, but not by cAMP, cGMP or calmodulin. High K* (30 mM) also stimulated the phosphorylation of this protein. Taurine blocks stimulation of the phosphorylation of the -20K M^ protein plus two other proteins with similar physical properties as shown on 2-D gels. However, the inhibitory effects of taurine on protein phosphorylation is not observed in the intrasynaptosomal cytosol but is present when the intrasynaptosomal cytosolic fraction is reconstituted with mitochondria. Ca** uptake in isolated mitochondria is stimulated by taurine in mediums with or without added ATP which consequently should result in reduced cytosolic Ca** levels. Taurine also inhibits the accumulation of ^^P labelled phosphatidic acid in synaptosomes thus producing a reduction in the cellular levels of diacylglycerol, a PKC activator. Therefore, it is hypothesized that taurine inhibits specific protein phosphorylation through indirect mechanisms involving the activity of certain isoz3nme(s) of PKC. These results suggest a functional role for taurine in the signal transduction regulatory process in the brain.