Abstract
We have previously reported the isolation by gel filtration and anionic exchange HPLC of two brain Na+, K+-ATPase inhibitors, II-A and II-E, and kinetics of enzyme interaction with the latter. In the present study we evaluated the kinetics of synaptosomal membrane Na+, K+-ATPase with II-A and found that inhibitory activity was independent of ATP (2–8 mM), Na+ (3.1–100 mM), or K+ (2.5–40 mM) concentration. Hanes-Woolf plots showed that II-A decreases Vmax in all cases; KM value decreased for ATP but remained unaltered for Na+ and K+, indicating respectively uncompetitive and noncompetitive interaction. However, II-A became a stimulator at 0.3 mM K+ concentration. It is postulated that brain endogenous factor II-A may behave as a sodium pump modulator at the synaptic region, an action which depends on K+ concentration.
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REFERENCES
Skou, J. C. 1957. The influence of same cations on an adenosine triphosphatase from peripheral nerves. Biochem. Biophys. Acta. 23:394-401.
Stahl, W. L. 1986. The Na+, K+-ATPase of nervous tissue. Neurochem. Int. 8:449-476.
Wu, P. H. 1986. Na+, K+-ATPase in nervous tissue. Pages 451-502, in Boulton, A. A., Baker, G. B., and Wu, P. H., (eds.), Neuromethods, Enzymes, vol. 5, Humana, Clifton, NJ
Albers, R. W., and Siegel, G. J. 1999. Membrane transport. Pages 95-118, in Siegel, G. J., Agranoff, B. W., Albers, R. W., Fisher, S. K., and Uhler, M. D. (eds.), Basic Neurochemistry, Lippincott-Raven, Philadelphia.
Rodríguez de Lores Arnaiz, G., Alberici, M., and De Robertis, E. 1967. Ultrastructural and enzymic studies of cholinergic and non-cholinergic synaptic membranes isolated from brain cortex. J. Neurochem. 14:215-225.
Rodríguez de Lores Arnaiz, G., and Antonelli de Gómez de Lima, M. 1986. Partial characterization of an endogenous factor which modulates the effect of catecholamines on synaptosomal Na+, K+-ATPase. Neurochem. Res. 11:933-947.
Rodríguez de Lores Arnaiz, G. 1992. In search of synaptosomal Na+, K+-ATPase regulators. Mol. Neurobiol. 6:359-375.
Rodríguez de Lores Arnaiz, G. 1993. An endogenous factor which interacts with synaptosomal membrane Na+, K+-ATPase activation by K+. Neurochem. Res. 18:655-661.
Rodríguez de Lores Arnaiz, G., and Peñ a, C. 1995. Characterization of synaptosomal membrane Na+, K+-ATPase inhibitors. Neurochem. Int. 27:319-327.
Herbin, T., Peñ a, C., and Rodríguez de Lores Arnaiz, G. 1998. Kinetics of Na+, K+-ATPase inhibition by a rat brain endogenous factor (II-E). Neurochem. Res. 23:33-37.
Albers, R. W., Rodríguez de Lores Arnaiz, G., and De Robertis, E. 1965. Sodium-potassium-activated ATPase and potassium-activated p-nitrophenylphosphatase: a comparison of their subcellular localizations in rat brain. Proc. Natn. Acad. Sci. USA 53:557-564.
Lowry, O. H., and Ló pez, J. A. 1946. Determination of inorganic phosphate in presence of labile P esters. J. Biol. Chem. 162:421-428.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. L. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265-275.
McGrail, K. M., Phillips, J. M., and Sweadner, K. J. 1991. Immunofluorescent localization of three Na+, K+-ATPase isozymes in the rat central nervous system: both neurons and glia can express more than one Na+, K+-ATPase. J. Neurosci. 11:381-391.
Antonelli, M., Casillas, T., and Rodríguez de Lores Arnaiz, G. 1991. Effect of Na+, K+-ATPase modifiers on high-affinitive ouabain binding determined by quantitative autoradiography. J. Neurosci. Res. 28:324-331.
Rodríguez de Lores Arnaiz, G. 1990. A study of tissue specificity of brain soluble fractions effect on Na+, K+-ATPase activity. Neurochem. Res. 15:289-294.
Lucking, K., and Nielsen, J. M. 1997. Abundance of α3, α2 and α1 isoforms of Na+, K+-ATPase in rat kidney as estimated by competitive RT-PCR and [3H]ouabain binding. Ann. N. Y. Acad. Sci. 834:107-109.
Goto, A., Yamada, K., Yagi, N., Yoshioka, M., and Sugimoto, T. 1992. Physiology and pharmacology of endogenous digital is like factors. Pharmacol. Rev. 44:377-399.
Hamlyn, J. M., Blaustein, M. P., Bova, S., DuCharme, D. W., Harris, D. W., Mandel, F., Mathews, W. R., and Ludens, J. H. (1991). Identification and characterization of a ouabain-like compound from human plasma. Proc. Natl. Acad. Sci. USA 88:6259-6263.
Mathews, W. R., Ducharme, D. W., Hamlym, J. M., Mandel, F., Clark, M. A., and Ludens, J. H. 1991. Mass spectral characterization of an endogenous digitalis-like factor from human plasma. Hypertension 17:930-935.
Fedorova, O. V., and Bagrov, A. Y. 1997. Inhibition of Na/K ATPase from rat aorta by two Na/K pump inhibitors, ouabain and marinobufagenin: evidence of interaction with different alpha-subunit isoforms. Am. J. Hypertens. 10:929-935.
Goto, A., and Yamada, K. 1998. Purification of endogenous digitalis-like factors from normal human urine. Clin Exp. Hypertens. 20:551-556.
Hamlyn, J. M. 1998. Observation of the nature, biosynthesis, secretion and significance of endogenous ouabain. Clin Exp. Hypertens. 20:523-533.
Tal, D. M., Yanuck, M. D., van Hall, G., and Karlish, S. J. D. 1989. Identification of Na+/K+-ATPase inhibitors in bovine plasma as fatty acids and hydrocarbons. Biochim. Biophys. Acta 985:55-59.
Bagrov, A. Y., Fedorova, O. V., Dmitrieva, R. Y., Howald, W. N., Hunter, A. P., Kuznetsova, E. A., and Shpen, V. M. 1998. Characterization of a urinary bufodienolide Na+, K+-ATPase inhibitor in patients after acute myocardial infarction. Hypertension 31:1097-1103.
Rodríguez de Lores Arnaiz, G., Reinés, A., Herbin, T., and Peñ a, C. 1998. Na+, K+-ATPase interaction with a brain endogenous inhibitor (endobain E). Neurochem. Int. 33:425-433.
Songu-Mize, E., Gunter, J. L., and Caldwell, R. W. 1989. Comparative ability of digoxin and an aminosugar cardiac glycoside to bind to and inhibit Na+, K+-adenosine triphosphatase. Effect of potassium. Biochem. Pharmacol. 38:3689-3695.
Peñ a, C., and Rodríguez de Lores Arnaiz, G. (1997) Differential properties between an endogenous brain Na+, K+-ATPase inhibitor and ouabain. Neurochem. Res. 22:379-383.
Akera, T., Wiest, S. A., and Brody, T. M. 1979. Differential effect of potassium on the action of digoxin and digoxigenin in guinea-pig heart. Eur. J. Pharmacol. 57:343-351.
Akera, T., Ng, Y.-C., Shieh, I.-S., Bero, E., Brody, T. M., and Braselton, W. E. 1985. Effects of K+on the interaction between cardiac glycosides and Na+, K+-ATPase. Eur. J. Pharmacol. 111: 147-157.
Ebner, F., and Mermi, J. 1991. The association with receptors regulates the Na+, K+-ATPase inhibitory potency of some cardioactive steroids. Eur. J. Pharmacol. 207:61-65.
Tamura, M., Harris, T. M., Konishi, F., and Inagami, T. 1993. Isolation and characterization of an endogenous Na+, K+-ATPasespecific inhibitor from pig urine. Eur. J. Biochem. 211:317-327.
Balzan, S., Ghione, S., Pieraccini, L., Biver, P., Di Bartolo, V., and Montali, U. 1994. Endogenous digitalis-like factor from umbilical cord and ouabain: comparison of biochemical properties. Pages 755-758, in Bamberg, E., and Schoner, W. (eds.), The Sodium Pump, Steinkopff, Darmstadt.
Norgaard, A., Kjeldsen, K., and Clausen, T. 1981. Potassium depletion decreases the number of 3H-ouabain binding sites and the active Na-K transport in skeletal muscle. Nature 293:739-741.
McDonough, A. A., Azuma, K. K:, Lescale-Matys, L., Tang, M.-J., Nakhoul, F., Hensley, C. B., and Komatsu, Y. 1992. Physiologic rationale for multiple sodium pump isoforms. Differential regulation of α1 vs α2 by ionic stimuli. Ann. N. Y. Acad. Sci. 671:156-169.
Schmidt, T. A., Larsen, J. S., and Kjeldsen, K. 1992. Quantification of rat cerebral cortex Na+, K+-ATPase: Effect of age and potassium depletion. J. Neurochem. 59:2094-2104.
Goto, A., and Yamada, K. 1998. Ouabain-like factor. Curr. Opin. Nephrol. Hypertens. 7:189-196.
Ferrandi, M., Manunta, P., Rivera, R., Bianchi, G., and Ferrari, P. 1998. Role of the ouabain-like factor and Na-K pump in rat and human genetic hypertension. Clin. Exp. Hypertens. 20: 629-639.
Van Huysse, J. W., and Leenen, F. H. 1998. Role of endogenous brain “ouabain” in the sympathoexcitatory and pressor effects of sodium. Clin. Exp. Hypertens. 20:657-667.
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Reinés, A., Peña, C. & Rodríguez de Lores Arnaiz, G. Kinetics of Na+-, K+-ATPase Inhibition by an Endogenous Modulator (II-A). Neurochem Res 25, 121–127 (2000). https://doi.org/10.1023/A:1007599718356
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DOI: https://doi.org/10.1023/A:1007599718356