Inhibition by taurine of the phosphorylation of specific synaptosomal proteins in the rat cortex: effects of taurine on the stimulation of calcium uptake in mitochondria and inhibition of phosphoinositide turnover.
It has been previously observed that taurine inhibits PKC-activated phosphorylation of specific proteins including a approximately 20k Mr protein in rat cortical synaptosomes. In the present study, the mechanism of the above effects of taurine were investigated. In an intrasynaptosomal cytosol fraction obtained by subcellular fractionation, taurine did not have inhibitory effects on protein phosphorylation. However, taurine did inhibit the phosphorylation of the approximately 20k Mr protein in a reconstituted preparation containing intrasynaptosomal cytosol and mitochondria. Experiments measuring calcium uptake demonstrated that taurine increased the accumulation of 45Ca2+ in the mitochondrial fraction in incubation systems both in the absence and presence of added ATP. In addition, taurine inhibited the accumulation of 32P-labeled phosphatidic acid in synaptosomes indicative of a reduction in the levels of diacylglycerol. These results suggest that taurine may inhibit specific protein phosphorylation both by reducing cytosolic calcium levels and by inhibiting the turnover of phosphoinositides. These effects of taurine on the signal transduction cascade involving PKC and phosphoinositide metabolism indicate a potential biological role for taurine in the nervous system.
Li
Y P
YP
Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock 79430.
Lombardini
J B
JB
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*; D013654:Taurine / Q000494:pharmacology*
D002132:Calcium Radioisotopes; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols; D013654:Taurine; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D002118:Calcium