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Journal of Biological Sciences

Year: 2006 | Volume: 6 | Issue: 6 | Page No.: 968-977
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Research Article

Effect of Drugs from the Class of Cardiac on the Na+, K+-ATPase Activity

Z.I.A. AL-Fifi

ABSTRACT

The effect of drugs from the class of cardiac (methyldigoxin, verapamil, propranolol), antiepileptic (carbamazepine), sedative (diazepam) and antihistaminic (promethazine) drugs on Na+, K+-ATPase activity of plasma membranes in rat brain synaptosomes was studied. Methyldigoxin in concentration of 0.1 mmol L-1 inhibits enzyme activity by 80%. Verapamil, propranolol and promethazine in concentrations of 20, 20 and 2 mmol L-1, respectively, inhibit entirely this ATPase activity. Carbamazepine and diazepam in concentrations of 0.02-60 mmol L-1 have no effect on the activity of this enzyme. According to drugs concentrations that inhibit 50% of enzyme activity (IC50), the potency order of drugs was: methyldigoxin >> promethazine > verapamil => propranolol. From inhibition of commercially available purified Na+, K+-ATPase isolated from porcine cerebral cortex in the presence of chosen drugs, as well as from the kinetic studies on synaptosomal plasma membranes, we may concluded that the drugs inhibit enzyme activity, in partly by acting directly on the enzyme protein. Propranolol, verapamil and promethazine inhibitions were in an uncompetitive manner. The results suggest that these three drugs may contribute to neurological dysfunction and point out to the necessity to take into consideration the side effects of the investigated drugs during the treatment of various pathological conditions.
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REFERENCES

  1. Acuna Castroviejo, D., C.M. del Aguila, B. Fernandez, M.D. Gomar and J.L. Castillo, 1992. Characterization of ouabain high-affinity binding to rat cerebral cortex. Modulation by melatonin. Eur. J. Pharmacol., 226: 59-67.
  2. Agarval, A., B.L. Tekwani, O.P. Shukla and S. Ghatak, 1990. Effect of anthelmintics and phenothiazines on adenosine 5'-triphosphatases of filarial parasite Setaria cervi. Ind. J. Exp. Biol., 28: 245-248.
  3. Albano, E., G. Bellomo, M. Parola, R. Carini and M.U. Dianzani, 1991. Stimulation of lipid peroxidation increases the intracellular calcium content of isolated hepatocytes. Biochim. Biophys. Acta, 1091: 310-316.
  4. Almotrefi, A.A., C. Basco, A. Moorji and N. Dzimiri, 1999. Class I antiarrhytmic drug effects on ouabain binding to guinea pig cardiac Na+-K+-ATPase. Can. J. Physiol. Pharmacol., 77: 866-870.
  5. Balzan, S., G. D'Urso, S. Ghione, A. Martinelli and U. Montali, 2000. Selective inhibition of human erythrocyte Na+/K+ ATPase by cardiac glycoside and by mammalian digitalis like factor. Life Sci., 67: 1921-1928.
    Direct Link
  6. Berrebi-Bertrand, I., J.M. Maixent, G. Christe and L.G. Levievre, 1990. Two active Na+/K+- ATPase of high affinity for ouabain in adult rat brain membranes. Biochim. Biophys. Acta, 1021: 148-156.
  7. Bloj, B., R.D. Morero, R.N. Faias R.E. and Trucco, 1973. Membrane lipid fatty acids and regulations of membrane-bound enzymes. Allosteric behavior of erythrocyte Mg2+-ATPase, (Na+K+)- ATPase and acetylcholinesterase from rats fed with different fat-supplemented diets. Biochem. Biophys. Acta, 311: 67-79.
  8. Bright, P.S., T.E. Gaffney, J.A. Street and J.G. Webb, 1985. Depolarization-induced release of propranolol and atenolol from rat cortical synaptosomes. Br. J. Pharmacol., 84: 499-510.
  9. Brines, M.L., A.O. Dare and N.C. De Lanerolle, 1995. The cardiac glycoside ouabain potentiates excitotoxic injury of adult neurons in rat hippocampus. Neurosci. Lett., 191: 145-148.
  10. Clatelain, P., R. Laruel, P. Vic and R. Brotelle, 1989. Differential effects of amidarone and propranolol on lipid dynamics and enzymatic activities in cardiac sarcolemmal membranes. Biochem. Pharmacol., 38: 1231-1239.
  11. Clausen, T. and J.A. Flatman, 1977. The effect of catecholamines on Na-K transport and membrane potential in rat soleus muscle. J. Physiol. (London), 270: 383-414.
  12. Dong, Z. and C.S. Xue, 1994. Effect of verapamil on Ca2+ and Ca(2+) Mg(2+)-ATPase activity in rat brain synaptosomes Zhongguo. Zao. Li. Xue. Bao., 15: 452-455.
  13. Dzuba, A., A. Breier, J. Slezak, T. Stankovicova, N. Vrbjar and A. Ziegelhoffer, 1991. Influence of calcium antagonists on heart sarcolemmal (N+ + K+)-ATPase Bratislav. Lek. Lisy., 92: 155-158.
  14. Eggl, P., K. Wirthensohn and H. Hirsch, 1986. Effects of hormones on phospholipid metabolism in human cultured fibroblasts. Biochim. Biophys. Acta, 862: 399-406.
  15. Ewart, H.S. and A. Klip, 1995. Hormonal regulation of the Na+-K+-ATPase: Mechanisms underlying rapid and sustained changes in pump activity Am. J. Physiol.-Cell Physiol., 269: C295-C311.
    Direct Link
  16. Forbush, B., 1982. Characterization of right-side-out membrane vesicles rich in (Na, K)-ATPase and isolated from dog kidney outer medulla. J. Biol. Chem., 257: 12678-12684.
  17. Gendron, F.P., J.G. Latour, D. Gravel, Y. Wang and A.R. Beaudoin, 2000. Ca2+ channel blockers and nucleoside triphosphate diphosphohydrolase (NTPDase) influence of diltiazem, nifedipine and verapamil. Biochem. Pharmacol., 60: 1959-1965.
  18. Gentile, D.A., C. Brown and D.P. Skoner, 1993. In vitro modulation of platelet sodium, potasium adenosine triphosphatase enzyme activity by antiallergy drugs. J. Lab. Clin. Med., 122: 85-91.
  19. Gerbi, A., J.M. Maixent, M. Zerouga, I. Berrebi-Bertrand, M. Debray, C. Chanez and J.M. Bourre, 1997. Specific modulation of two neuronal digitalis receptors by anaesthesia. J. Recept. Signal. Transduct. Res., 17: 137-147.
  20. Gill, D.L., S.H. Chuen, M.W. Noel and T. Ueda, 1986. Orientation of synaptic plasma membrane vesicles containing calcium pump and sodium-calcium exchange activities. Biochim. Biophys. Acta, 856: 165-173.
  21. Gopalaswamy, U.V., J.G. Satav, S.S. Katyare and R.K. Bhattacharya, 1997. Effect of propranolol on rat brain synaptosomal Na+-K+-ATPase, Mg2+-ATPase and Ca2+-ATPase. Chem. Biol. Interac., 103: 51-58.
  22. Grisar, T., 1984. Glial and neuronal Na+, K+ pump in epilepsy. Ann. Neurol., 16: 128-134.
  23. Hendrikse, N.H., A.H. Schinkel, E.G.E. Devries, E. Fluks and W.T.A. van Der Graaf et al., 1998. Complete in vivo reversal of P-glycoprotein pump function in the blood-brain barrier visualized with positron emission tomography. Br. J. Pharmacol., 124: 1413-1418.
  24. Herrera, V.L.M., J.R. Emanuel, N. Ruiz-Opazo, R. Levenson and G. Nadal, 1987. Three differentially expressed Na+, K+-ATPase α subunit isoforms: Structural and functional implications. Can. J. Physiol. Pharmacol., 55: 1098-1101.
  25. Hoechen, R.J., 1977. Effects of verapamil on (Na++K+)-ATPase, Ca2+-ATPase and adenylate cyclase activity in membrane fraction from rat and guinea pig ventricular muscle. Can. J. Physiol. Pharmacol., 55: 1098-1101.
  26. Horvat, A., G. Nikezif and J. Martinovif, 1995. Estradiol binding to synaptosomal plasma membranes of rat brains. Experientia, 51: 11-15.
  27. Jewell, E.A., O.I. Shamraj and J.B. Lingrel, 1992. Isoforms of the α subunit of Na+, K+-ATPase and their significance. Acta Physiol. Scand., 146: 161-169.
  28. Jortani, A.S. and J.R. Valders, 1997. Digoxin and its related endogenous factors. Clin. Lab. Sci., 34: 225-274.
  29. Kim, H.C. and B.U. Raess, 1988. Verapamil, diltiazem and nifedipine interaction with calmodulin stimulated (Ca2+ + Mg2+)-ATPase. Biochem. Pharmoacol., 37: 917-920.
  30. Kinne-Saffran, E. and R.K.H. Kinne, 2001. Inhibition by mercuric chloride of Na-K-2Cl cotransport activity in rectal gland plasma membrane vesicles isolated from Squalus acanthias. Biochim. Biophys. Acta, 1510: 442-451.
  31. Lees, G.J., 1991. Inhibition of sodium-potassium ATPase: A potentially ubiquitous mechanism contributing to central nervous system neuropathology. Brain Res. Rev., 16: 283-300.
  32. Lees, G.J., 1993. Contributory mechanisms in the causation of neurodegenerative disorders. Neuroscience, 54: 287-322.
    CrossRefPubMed
  33. Li, P.W., C.S. Ho and R. Swaminathan, 1993. The chronic effects of long-term digoxin administration on Na+/K+-ATPase activity in rat tissues. Intl. J. Cardiol., 40: 95-100.
  34. Lingrel, J.B., M.L. Croyle, A.L. Woo and J.M. Arguello, 1998. Ligand binding sites of Na, K- ATPase. Acta Physiol. Scand., 163: 69-77.
  35. Lopez, L.B., L.E.M. Quintas and F. Noel, 2002. Influence of development on Na+/K+-ATPase expression: Isoform- and tissue-dependency. Comp. Biochem. Physiol., 131: 323-333.
  36. Mariyama, Y., H.L. Tsai M. Futai, 1993. Energy dependent accumulation of neuron blockers causes selective inhibition of neurotransmitter uptake by brain synaptic vesicles. Arch. Biochem. Biophys., 305: 278-281.
  37. Mazzoni, M.R., C. Martini and A. Lucacchini, 1990. [3H]ouabain binding to ox brain membranes: Characterization of a high-affinity binding site. Neurochem. Int., 16: 193-197.
  38. Murakami, A. and T. Furvi, 1994. Effects of the connectional anticonvulsants, phenytoin, carbamazepine and valproic acid, on sodium-potassium-adenosine triphosphatase in acute ischemic brain. Neurosurgery, 34: 1047-1051.
  39. Myers, M.G., P.J. Lewis, J.L. Reid and C.T. Dollery, 1975. Brain concentration of propranolol in relation to hypertensive effect in the rabbit with observations on brain propranolol levels in man. Pharmocol. Exp. Therat., 192: 327-335.
  40. Nagy, A.K., C.R. Houser and A.V. Delgado-Escueta, 1990. Synaptosomal ATPase activities in temporal cortex and hippocampal formation of humans with focal epilepsy. Brain Res., 529: 192-201.
  41. Nosal, R., V. Jancinova, K. Ornias, J. Jakubovsky and P. Balgavy, 1985. The interaction of beta-adrenoceptor blocking. Biochim. Biophys. Acta, 821: 217-228.
  42. Ondrias, K., P. Balgavy, S. Stolc and L.I. Horvath, 1983. A spin label study of the perturbation effects of tertiary amine anesthetics on bran lipid liposomes and synaptosomes. Biochim. Biophys. Acta, 732: 627-635.
  43. Ondrias, K., A. Stasko, Jancinovav and P. Balgavy, 1987. Comparison of effects of eleven beta-adrenoceptor blocking drugs in perturbing lipid membranes: An ESR spectroscopy study. Mol. Pharmacol., 31: 97-102.
  44. Ondrias, K., A. Stasko, V. Marko and R. Nosal, 1989. Influence of beta-adrenoceptor blocking drugs on lipid-protein interaction in synaptosomal membranes. An ESR study. Chem. Biol. Interact., 69: 87-97.
  45. Ondrias, K., A. Stasko, V. Misik, J. Reguli and E. Svajdlenka, 1991. Comparation of perturbation effect of propranolol, verapamil, chloropromazine and carbisocaine on lecithin liposomes and brain total lipid liposomes. An EPR spectroscopy study. Chem. Biol. Ineract., 79: 197-206.
  46. Ondrias, K., E. Ondriasova and A. Stasko, 1992. Perturbation effects of eight calcium channel blockers on liposomal membranes prepared from rat brain total lipids. Chem. Phys. Lipids, 62: 11-17.
  47. Ondriasova, E., K. Ondrias, A. Stasko, R. Nosal and J. Csollei, 1992. Comparation of the potency of five beta-adrenoceptor blocking drugs and eight calcium channel blockers to inhibit platelet aggregation and to perturbe liposomal membranes prepared from platelet lipids. Physiol. Res., 41: 267-272.
  48. Paglini-Oliva, P. and H.W. Rivarola, 2003. Central nervous system agents used as trypanosoma crusi infection chemotherapy: Phenothiazines and related compounds. Curr. Med. Chem. Antiinfec. Agents, 2: 323-333.
  49. Park, T.M., 1994. Abnormal cortical unit activity of the reticular formation. Electromyogr. Clin. Neurophysiol., 34: 427-435.
  50. Pekovic, S., G. Nikezic, A. Horvat and R. Metlas, 1986. A high affinity calcium-stimulated ATPase in synaptic plasma membranes detected in the presence and absence of exogenous magnesium. Brai. Res., 379: 251-256.
  51. Pekovic, S., N. Nedeljkovic, G. Nikezic, A. Horvat, M. Stojiljkovic, L. Rakic and J.V. Martinovic, 1997. Biochemical characterization of the hippocampal and striatal Na,K-ATPase reveals striking differences in kinetic properties. Gen. Physiol. Biophys., 16: 227-240.
    PubMedDirect Link
  52. Raess, B.U. and M.H. Gerstten, 1987. Calmodulin-stimulated plasma membrane (Ca2+ + Mg2+)-ATPase: Inhibition by calcium channel entry blockers. Biochem. Pharmacol., 36: 2455-2459.
  53. Raess, B.U. and D.M. Record, 1990. Inhibition of erythrocyte Ca2+-pump by Ca2+ antagonists. Biochem. Pharmacol., 40: 2549-2555.
  54. Repke, K.R.H., R. Megges, J.M. Weiland and R. Schon, 1995. Location and properties of the digitalis receptor site in Na+/K+- ATPase. FEBS. Lett., 359: 107-109.
  55. Rodriguez de Lores Arnaiz, G. and C. Pena, 1995. Characterization of synaptosomal membrane Na+, K+-ATPase inhibitors. Neurochem. Int., 27: 319-327.
    CrossRefDirect Link
  56. Rodriguez, M.A., M. Padron-Nieves, M. Perez-Gonzalez and G. Lamanna, 1994. Effect of the in vivo administration of beta-methyldigoxin on the Na+, K+-ATPase measured in different tissues of guinea pigs. Acta Cient. Venez., 45: 112-119.
  57. Schroeder, F., R.N. Fontaine, D.J. Feeler and K.G. Weston, 1981. Drug-induced surface membrane phospholipid composition in murine fibroblasts. Biochim. Biophys. Acta, 643: 76-88.
  58. Shi, B. and H.T. Tien, 1986. Action of calcium channel and beta-adrenergic blocking agents in bilayer lipid membranes. Biochim. Biophys. Acta, 859: 125-134.
  59. Srivastava, M. and S.S. Katyare, 1983. The effect of propranolol on rat brain catecholamine biosynthesis. J. Biosci., 5: 261-266.
  60. Street, J.A., J.G. Webb, P.S. Bright and T.E. Gaffney, 1984. Accumulation, subcellular localization and release of propranolol from synaptosomes of rat cerebral cortex. J. Pharmacol. Exp. Ther., 229: 154-161.
  61. Sweadner, K.J., 1985. Enzymatic properties of separated isozymes of the Na,K-ATPase. J. Biol. Chem., 260: 11508-11513.
  62. Towle, A.C. and P.Y. Sze, 1983. Steroid binding to synaptic plasma membrane: Differential binding of glucocorticoid and gonadal steroids. J. Steroid. Biochem., 18: 135-143.
  63. Weitman, S.D., A.M. Phelan, J.J. Lech and D.G. Lange, 1989. Propranolol-induced alterations in rat erythrocyte membrane fluidity and apparent phase-transition temperatures. A depth-dependent process. Biocem. Pharmacol., 38: 2949-2955.
  64. Whikehart, D.R., B. Montgomery, D.H. Sorna and J.D. Wells, 1991. Beta-bloking agents inhibit N+K+ATPase in cultured corneal endothelial and epithelial cells. J. Ocul. Pharmacol., 7: 195-200.
  65. Wyse, A.T.S., E.L. Streck, P. Worm, A. Wajner, F. Ritter and C.A. Netto, 2000. Preconditioning prevents the inhibition of Na+,K+-ATPase activity after brain ischemia. Neurochem. Res., 25: 969-973.
  66. Yamamoto, M. and H. Aki, 1991. Flow microcalorimetry for human erythrocyte hemolysis induced by ionic drug binding. Thermochimica. Acta, 193: 287-297.

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