AN ENDOGENOUS FACTOR WHICH INTERACTS WITH SYNAPTOSOMAL MEMBRANE NA+, K+-ATPASE ACTIVATION BY K+

In previous papers, the isolation of brain soluble fractions able to modify neuronal Na+, K+-ATPase activity has been described. One of those fractions-peak I-stimulates membrane Na+, K+-ATPase while another-peak II-inhibits this enzyme activity, and has other ouabain-like properties. In the present study, synaptosomal membrane Na+, K+-ATPase was analyzed under several experimental conditions, using ATP or p-nitrophenylphosphate (p-NPP) as substrate, in the absence and presence of cerebral cortex peak II. Peak II inhibited K+-p-NPPase activity in a concentration dependent manner. Double reciprocal plots indicated that Peak II uncompetitively inhibits K+-p-NPPase activity regarding substrate, Mg2+ and K+ concentration. Peak II failed to block the known K+-p-NPPase stimulation caused by ATP plus Na+. At various K+ concentrations, percentage K+-p-NPPase inhibition by peak II was similar regardless of the ATP plus Na+ presence, indicating lack of correlation with enzyme phosphorylation. Na+, K+-ATPase activity was decreased by peak II depending on K+ concentration. It is postulated that the inhibitory factor(s) present in peak II interfere(s) with enzyme activation by K+.