Digitalis-like properties of an inhibitor of the Na+/K+ pump in human cerebrospinal fluid.
Work originally reported by my laboratory has established that a constituent of human cerebrospinal fluid (CSF) specifically inhibits the Na+/K+ pump in human red cells and the activity of the enzyme (Na+/K+)-ATPase. Furthermore, we have shown that the inhibitory compound has a molecular weight of approx. 600 and is sensitive to proteolytic digestion, indicating that it is a small peptide. I describe here that the inhibitor of the Na+/K+ pump in human CSF mimics the effects the digitalis glycosides in 3 different assay systems: the Na+/K+ pump in human red cell, the (Na+/K+)-ATPase activity of a purified enzyme and the specific binding of [3H]ouabain to its receptor in the red cell membrane. Moreover, the inhibitor in human CSF is a competitive inhibitor of the stimulation of the Na+/K+ pump by extracellular K+. Based on these findings, I propose that a small peptide with digitalis-like properties present in human CSF is an endogenous regulator of the Na+/K+ pump in cells of the central nervous system. This digitalis-like substance could be one factor regulating the K+ concentration of the CSF and controlling the secretion of CSF by the choroid plexus.
Halperin
J A
JA
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
D000328:Adult; D001667:Binding, Competitive; D004070:Digitalis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000134:cerebrospinal fluid*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007223:Infant; D008970:Molecular Weight; D010042:Ouabain / Q000378:metabolism; D010946:Plants, Medicinal; D010947:Plants, Toxic; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013820:Thermolysin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010042:Ouabain; D013820:Thermolysin; D000254:Sodium-Potassium-Exchanging ATPase