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Modulation of the Ca2+ pump by the hypothalamic-hypophysary inhibitory factor.

We previously purified to homogeneity an endogenous sodium pump inhibitor from bovine hypothalamus and hypophysis that is different from digoxin or ouabain and studied the effects of this factor on the total Ca2+,Mg(2+)-ATPase activity of plasma membrane of synaptosomes. This factor inhibits the calcium pump and the total Mg(2+)-ATPase activity of these membranes with approximately the same K0.5 values of inhibition. The potency of this factor as an inhibitor depends on the membrane concentration in the assay medium. The inhibition of the magnesium-dependent ATPase activities of these membranes was of a noncompetitive type with respect to the substrate Mg(2+)-ATP and did not significantly shift the calcium dependence of the Ca2+,Mg(2+)-ATPase activity. We suggest that the calcium pump of the synaptosomal plasma membrane is inhibited by this factor through disruption of the lipid annulus; this inhibition could play a role in the control of calcium homeostasis by increasing the cytosolic free calcium concentration.