NA-ATPASE IN THE CHOROID-PLEXUS - REGULATION BY SEROTONIN PROTEIN-KINASE-C PATHWAY(,K+)

In the choroid plexus, the ion pump Na+,K+-ATPase regulates the produc tion of cerebrospinal fluid. We now report that incubation of choroid plexus with an activator of protein kinase C, phorbol 12,13-dibutyrate , strongly stimulates the phosphorylation of Na+,K+-ATPase and inhibit s its activity. Similar effects were obtained with serotonin, which in the choroid plexus stimulates phosphoinositide turnover, thereby acti vating protein kinase C. Serotonin (10 mu M) increased by about 10-fol d the amount of phosphorylated Na+,K+-ATPase and significantly reduced its activity. Two-dimensional peptide mapping showed comigration of N a+,K+-ATPase phosphorylated by either phorbol 12,13-dibutyrate or sero tonin in intact cells and by protein kinase C in vitro. These results demonstrate that first messengers can regulate the activity of Na+,K+- ATPase through a mechanism involving protein phosphorylation. Moreover , they provide a plausible mechanism for the demonstrated ability of s erotonin to decrease cerebrospinal fluid production.