Activation of Na,K-ATPase by an endogenous peptide, PEC-60

Several peptidic and non-peptidic factors can modulate Na,K-ATPase activity, among them mainly inhibitors of this enzyme, ouabain being the most effective. In a very few cases only, activation of Na,K-ATPase by endogenous factors has been recorded. We have investigated the effect on Na,K-ATPase of a novel regulatory peptide, PEC-60, recently isolated from porcine intestine. Various biological effects have been described for PEC-60 in different tissues, including brain. We have found that PEC-60 caused a dose-dependent activation of Na,K-ATPase from rat brain frontal cortex, whereas the carboxymethylated form of PEC-60 or other hormonal peptides had no effect. The maximal value of activity reaches up to 125% at close to micromolar concentrations of PEC-60 and the dependence can be described with a bell-shaped curve, indicating a complex mechanism for the interaction. The activation of the enzyme by PEC-60 is apparently related to Na(+)-dependent steps of the Na,K-ATPase system. The kinetic parameters for K(+)-phosphatase were unaffected. Moreover, the activating effect was enhanced by preincubation at low concentrations of ATP that transform the enzyme into the Na(+)-form. Due to the crucial physiological role of Na,K-ATPase, its activity has to be finely controlled and thus PEC-60 may be one of the endogenous factors that regulate this enzyme.