Demonstration of an endogenous activator for the Na+, K(+)-ATPase system.

A heat-labile, non-dialysable and protease-sensitive endogenous activator (NaAF) capable of stimulating the Na+, K(+)-ATPase system has been demonstrated. The activator (NaAF) activity was partially enriched (about 10 fold) by dialysis (30 kDa cutoff) under negative pressure and pH 4.8 precipitation. The NaAF has been found to occur in the cytosolic fractions of tissues such as the kidney and brain from two different species (rabbit and pig) tested so far. Also, the factor from one tissue stimulates with equal efficacy the Na+, K(+)-ATPase systems of other tissues regardless of the species; thus demonstrating universal nature of the activator. Some degree of cross-reactivity was noted between the activating effects of this activator (for the Na+,K(+)-ATPase) and that for the H+,K(+)-ATPase recently described (J. Biol. Chem. 262:5664-5670, 1987). The purified NaAF obtained from sephacryl S-300 column chromatography activates the pure renal medullary Na+,K(+)-ATPase in a dose dependent manner.