REGULATION BY PHORBOL ESTERS OF THE GLYCINE TRANSPORTER (GLYT1) IN GLIOBLASTOMA CELLS

The high-affinity glycine transporter in neurons and glial cells is th e primary means of inactivating synaptic glycine. The effects of 12-O- tetradecanoylphorbol ester (TPA), a potent activator of protein kinase C (PKC), on the high-affinity Na+-dependent glycine transport were in vestigated in C6 cells, a cell line of glial origin. Incubation of C6 cells with TPA led to concentration- and time-dependent decrease in th e glycine transport that could be completely suppressed by the additio n of the PKC inhibitor staurosporine. The TPA effect could be mimicked by oleoylacetylglycerol and exogenous phospholipase C. Northern and W estern blot analysis indicate that C6 cells express the GLYT1 glycine transporter. Incubation of COS cells transiently transfected with a fu ll-length clone of the GLYT1 transporter in the presence of TPA, produ ces a decrease in glycine uptake.