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Investigation of the cellular mechanisms of actions of digoxin and monensin by using guinea-pig papillary muscles

Year 2009, Volume: 3 Issue: 3, 1 - 5, 01.11.2009

Abstract

This experiment was carried out to determine the possible mechanism of actions of monensin and digoxin by using guinea-pig papillary muscles. A total of 120 papillary muscles obtained from 60 guinea-pigs were used. Three treatment groups; control (%0,1 ethanol), monensin (10 μmol/l) and digoxin (3 μmol/l) were compared in normal, Na+-free, Ca2+-free, and thapsigargin-added Krebs solutions. It was found that both digoxin and monensin caused a positive inotropic effect in normal and Ca2+-free Krebs solutions. Although monensin produced a positive inotropic effect in thapsigargin-treated papillary muscles, digoxin did not show a positive inotropic effect. Because papillary muscles in Na+ -free Krebs solution showed spontaneous contractions, trusted results were not obtained in Na+ -free medium. It is concluded that monensin produces a positive inotropic effect by depending on both extracellular Ca2+ and Ca2+ released from the sarcoplasmic reticulum (SR). Digoxin, on the other hand, produces its effect by depending on the Ca2+ released from SR.

References

  • Balzan, S., G. D’Urso, S. Ghione, A. Martinelli, and U. Montali, 2000: Selective inhibition of human erythrocyte Na+/K+ ATPase by cardiac glycosides and by a mammalian digitalis like factor. Life Sci. 67, 1921–1928.
  • Barry, W. H., and J. H. B. Bridge, 1993: Intracellularr calcium homeostasis in cardiac myocytes. Circulation 87, 1806–1815.
  • Deitmer, J. W., and D. Ellis, 1978: Intracellular sodium activity of cardiac purkinje fibers during inhibition and reactivation of the Na-K pump. J. Physiol. (Lond.) 284, 241–259.
  • Ehara, T., A. Noma, and K. Ono, 1988: Calcium-activated non-selective cation channel in ventricular cells isolated from adult guinea-pig hearts. J. Physiol. (Lond.) 403, 117–133.
  • Fabiato, A., 1985: Simulated calcium current can both cause calcium loading in and trigger calcium release from sarcoplasmic reticulum of a skinned canine cardiac purkinje cell. J. Gen. Physiol. 85, 291–320.
  • Hugtenburg, J. G., M. J. Mathy, J. J. Beckeringh, and P. A. Van Zwiten, 1989: The differential effect of calcium antagonists on the positive inotropic effects induced by calcium and monensin in cardiac preparations of rats and guinea-pigs. Naunyn-Schmiedeberg’s Arch. Pharmacol. 340, 558–566.
  • Meral, I., 1998: Effects of different concentrations of Monensin on the contractility changes of guinea-pig papillary muscles. Tr. J. Vet. Ani. Sci. 22, 145–149.
  • Meral, I., Hembrough, F. B., Bailey, T. B., and W. Hsu, 2002a: Functional changes in isolated guinea-pig papillary muscle induced by monensin and digoxin. J. Vet. Med. A Physiol. Pathol. Clin. Med. 49(1), 51-56.
  • Meral, I., Hsu, W., and F. B., Hembrough, 2002b: Digoxin- and monensin-induced changes of intracellular Ca2+ concentration in isolated guinea-pig ventricular myocyte. J. Vet. Med. A Physiol. Pathol. Clin. Med. 49(6), 329-333.
  • Miura, D. S., and S. Biedert, 1985: Cellular mechanisms of digitalis action. J. Clin. Pharmacol. 25, 490–500.
  • Mollenhauer, H. H., D. J. Morre, and L. D. Rowe, 1990: Alteration of intracellular traffic by monensin; mechanism, specificity and relationship to toxicity. Biochim. Biophys. Acta 1031, 225–246.
  • Muller-Ehmsen, J., K. Frank, K. Brixius, and R. H. Schwinger, 1997: Increase in force of contraction by activation of the Na+/Ca (2+)-exchanger in human myocardium. Br. J. Clin. Pharmacol. 43, 399–405.
  • Nagai, K., T. Murakami, T. Iwase, T. Tomita, and S. Sasayama, 1996: Digoxin reduces beta-adrenergic contractile response in rabbit hearts. Ca (2+)-dependent inhibition of adenylyl cyclase activity via Na+/Ca2+ exchange. J. Clin. Invest. 97, 6–13.
  • Satoh, H., and K. Tsuchida, 1999: Pharmacological actions of monovalent ionophores on spontaneously beating rabbit sino-atrial nodal cells. Gen. Pharmacol. 33, 151–159.
  • Snedecor, G. W., and W. G. Cochran, 1989: Statistical Methods, 8th edn, pp. 227. Iowa State University Press, Ames, IA, USA.
  • Somberg, J., and B. Greenfield, 1985: Digitalis: Historical development in clinical medicine. J. Clin. Pharmacol. 25, 484–489.
  • Tsuchida, K., and S. Otomo, 1990: Electrophysiological effects of monensin, a sodium ionophore, on cardiac purkinje fibers. Eur. J. Pharmacol. 190, 313–320.
Year 2009, Volume: 3 Issue: 3, 1 - 5, 01.11.2009

Abstract

References

  • Balzan, S., G. D’Urso, S. Ghione, A. Martinelli, and U. Montali, 2000: Selective inhibition of human erythrocyte Na+/K+ ATPase by cardiac glycosides and by a mammalian digitalis like factor. Life Sci. 67, 1921–1928.
  • Barry, W. H., and J. H. B. Bridge, 1993: Intracellularr calcium homeostasis in cardiac myocytes. Circulation 87, 1806–1815.
  • Deitmer, J. W., and D. Ellis, 1978: Intracellular sodium activity of cardiac purkinje fibers during inhibition and reactivation of the Na-K pump. J. Physiol. (Lond.) 284, 241–259.
  • Ehara, T., A. Noma, and K. Ono, 1988: Calcium-activated non-selective cation channel in ventricular cells isolated from adult guinea-pig hearts. J. Physiol. (Lond.) 403, 117–133.
  • Fabiato, A., 1985: Simulated calcium current can both cause calcium loading in and trigger calcium release from sarcoplasmic reticulum of a skinned canine cardiac purkinje cell. J. Gen. Physiol. 85, 291–320.
  • Hugtenburg, J. G., M. J. Mathy, J. J. Beckeringh, and P. A. Van Zwiten, 1989: The differential effect of calcium antagonists on the positive inotropic effects induced by calcium and monensin in cardiac preparations of rats and guinea-pigs. Naunyn-Schmiedeberg’s Arch. Pharmacol. 340, 558–566.
  • Meral, I., 1998: Effects of different concentrations of Monensin on the contractility changes of guinea-pig papillary muscles. Tr. J. Vet. Ani. Sci. 22, 145–149.
  • Meral, I., Hembrough, F. B., Bailey, T. B., and W. Hsu, 2002a: Functional changes in isolated guinea-pig papillary muscle induced by monensin and digoxin. J. Vet. Med. A Physiol. Pathol. Clin. Med. 49(1), 51-56.
  • Meral, I., Hsu, W., and F. B., Hembrough, 2002b: Digoxin- and monensin-induced changes of intracellular Ca2+ concentration in isolated guinea-pig ventricular myocyte. J. Vet. Med. A Physiol. Pathol. Clin. Med. 49(6), 329-333.
  • Miura, D. S., and S. Biedert, 1985: Cellular mechanisms of digitalis action. J. Clin. Pharmacol. 25, 490–500.
  • Mollenhauer, H. H., D. J. Morre, and L. D. Rowe, 1990: Alteration of intracellular traffic by monensin; mechanism, specificity and relationship to toxicity. Biochim. Biophys. Acta 1031, 225–246.
  • Muller-Ehmsen, J., K. Frank, K. Brixius, and R. H. Schwinger, 1997: Increase in force of contraction by activation of the Na+/Ca (2+)-exchanger in human myocardium. Br. J. Clin. Pharmacol. 43, 399–405.
  • Nagai, K., T. Murakami, T. Iwase, T. Tomita, and S. Sasayama, 1996: Digoxin reduces beta-adrenergic contractile response in rabbit hearts. Ca (2+)-dependent inhibition of adenylyl cyclase activity via Na+/Ca2+ exchange. J. Clin. Invest. 97, 6–13.
  • Satoh, H., and K. Tsuchida, 1999: Pharmacological actions of monovalent ionophores on spontaneously beating rabbit sino-atrial nodal cells. Gen. Pharmacol. 33, 151–159.
  • Snedecor, G. W., and W. G. Cochran, 1989: Statistical Methods, 8th edn, pp. 227. Iowa State University Press, Ames, IA, USA.
  • Somberg, J., and B. Greenfield, 1985: Digitalis: Historical development in clinical medicine. J. Clin. Pharmacol. 25, 484–489.
  • Tsuchida, K., and S. Otomo, 1990: Electrophysiological effects of monensin, a sodium ionophore, on cardiac purkinje fibers. Eur. J. Pharmacol. 190, 313–320.
There are 17 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Ramazan Üstün

İsmail Meral This is me

Publication Date November 1, 2009
Published in Issue Year 2009 Volume: 3 Issue: 3

Cite

APA Üstün, R., & Meral, İ. (2009). Investigation of the cellular mechanisms of actions of digoxin and monensin by using guinea-pig papillary muscles. Journal of Applied Biological Sciences, 3(3), 1-5.
AMA Üstün R, Meral İ. Investigation of the cellular mechanisms of actions of digoxin and monensin by using guinea-pig papillary muscles. J.appl.biol.sci. November 2009;3(3):1-5.
Chicago Üstün, Ramazan, and İsmail Meral. “Investigation of the Cellular Mechanisms of Actions of Digoxin and Monensin by Using Guinea-Pig Papillary Muscles”. Journal of Applied Biological Sciences 3, no. 3 (November 2009): 1-5.
EndNote Üstün R, Meral İ (November 1, 2009) Investigation of the cellular mechanisms of actions of digoxin and monensin by using guinea-pig papillary muscles. Journal of Applied Biological Sciences 3 3 1–5.
IEEE R. Üstün and İ. Meral, “Investigation of the cellular mechanisms of actions of digoxin and monensin by using guinea-pig papillary muscles”, J.appl.biol.sci., vol. 3, no. 3, pp. 1–5, 2009.
ISNAD Üstün, Ramazan - Meral, İsmail. “Investigation of the Cellular Mechanisms of Actions of Digoxin and Monensin by Using Guinea-Pig Papillary Muscles”. Journal of Applied Biological Sciences 3/3 (November 2009), 1-5.
JAMA Üstün R, Meral İ. Investigation of the cellular mechanisms of actions of digoxin and monensin by using guinea-pig papillary muscles. J.appl.biol.sci. 2009;3:1–5.
MLA Üstün, Ramazan and İsmail Meral. “Investigation of the Cellular Mechanisms of Actions of Digoxin and Monensin by Using Guinea-Pig Papillary Muscles”. Journal of Applied Biological Sciences, vol. 3, no. 3, 2009, pp. 1-5.
Vancouver Üstün R, Meral İ. Investigation of the cellular mechanisms of actions of digoxin and monensin by using guinea-pig papillary muscles. J.appl.biol.sci. 2009;3(3):1-5.