Proline administration decreases Na+,K+-ATPase activity in the synaptic plasma membrane from cerebral cortex of rats

Buffered proline was injected subcutaneously into rats twice a day at 8 h i ntervals from the 6(th) to the 28(th) day of age. Control rats received sal ine in the same volumes. The animals were weighed and killed by decapitatio n 12 h after the last injection. Cerebral cortex was used for the determina tion of Na+,K+-ATPase and Mg2+-ATPase activities. Body, whole brain and cor tical weights were similar in the two groups. Na+,K+-ATPase activity was si gnificantly reduced (by 20%) in membranes from the proline-treated group co mpared to the controls, whereas Mg2+-ATPase activity was not affected by pr oline. In another set of experiments, synaptic plasma membranes were prepar ed from cerebral cortex of 29-day-old rats and incubated with proline at fi nal concentrations ranging from 0.1 to 2.0 mM. Na+,K+-ATPase activity, but not Mg2+-ATPase activity, was inhibited by 20-30%. Since proline concentrat ions in plasma of chronically treated rats and of type 11 hyperprolinemic c hildren are of the same order of magnitude as those tested in vitro, the re sults suggest that reduction of Na+,K+-ATPase activity may contribute to th e neurological dysfunction found in some patients affected by type 11 hyper prolinemia.