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Effect of carticaine on the sarcoplasmic reticulum Ca2+-adenosine triphosphatase. II. Cations dependence

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Abstract

Ca2+-ATPase is a major intrinsic protein in the sarcoplasmic reticulum (SR) from skeletal muscles. It actively transports Ca2+ from the cytoplasm to the SR lumen, reducing cytoplasmic [Ca2+] to promote muscle relaxation. Carticaine is a local anesthetic widely used in operative dentistry. We previously showed that carticaine inhibits SR Ca2+-ATPase activity and the coupled Ca2+ uptake by isolated SR vesicles, and increases the rate of Ca2+ efflux from preloaded vesicles. We also found that these effects were antagonized by divalent cations, and concluded that they were mainly due to the direct interaction of carticaine with the Ca2+-ATPase protein. Here we present additional results on the modulation of the above effects of carticaine by Ca2+ and Mg2+. The activating effect of Ca2+ on the ATPase activity is competitively inhibited by carticaine, indicating a decreased Ca2+ binding to the high affinity Ca2+ transport sites. The activating effect of Mg2+ on the phosphorylation of Ca2+-ATPase by orthophosphate is also inhibited by carticaine. The anesthetic does not affect the reaction mechanism of the cations acting as cofactors of ATP in the catalytic site. On the basis of the present and our previous results, we propose a model that describes the effect of carticaine on the Ca2+-ATPase cycle.

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Abbreviations

SR:

Sarcoplasmic reticulum

Ca-ATPase:

Calcium dependent adenosine triphosphatase

MOPS:

3-[N-morpholino]propane-sulfonic acid

MES:

2-[N-Morpholino]ethanesulfonic acid

References

  • Alonso GL, Takara D, González DA (1990) Direct demonstration of an acid-labile phosphoenzyme in the cycle of the sarcoplasmic reticulum Ca2+-dependent adenosinetriphosphatase. Biochim Biophys Acta 1030:172–175

    CAS  PubMed  Google Scholar 

  • Alonso GL, González DA, Takara D, Ostuni MA, Sánchez GA (1998) Calcium additional to that bound to the transport sites is required for full activation of the sarcoplasmic reticulum Ca-ATPase from skeletal muscle. Biochim Biophys Acta 1405:47–54

    Article  CAS  PubMed  Google Scholar 

  • Alonso GL, González DA, Takara D, Ostuni MA, Sánchez GA (2001) Kinetic analysis of a model of the sarcoplasmic reticulum Ca-ATPase, with variable stoichiometry, which enhances the amount and the rate of Ca transport. J Theor Biol 208:251–260

    Article  CAS  PubMed  Google Scholar 

  • Baginski ES, Foa PP, Zak B (1967) Determination of phosphate: study of labile organic phosphate interference. Clin Chim Acta 15:155–158

    Article  CAS  Google Scholar 

  • Champeil P, Guillain F, Venien C, Gingold PM (1985) Interaction of magnesium and inorganic phosphate with calcium-deprived sarcoplasmic reticulum adenosine-triphosphatase as reflected by organic solvent induced perturbation. Biochemistry 24:69–81

    Article  CAS  PubMed  Google Scholar 

  • De Meis L (1972) Phosphorylation of the membranous protein of the sarcoplasmic reticulum. Inhibition by Na+ and K+. Biochemistry 11:2460–2465

    Article  PubMed  Google Scholar 

  • De Meis L (1976) Regulation of steady state level of phosphoenzyme and ATP synthesis in sarcoplasmic reticulum vesicles during reversal of the Ca2+ pump. J Biol Chem 251:2055–2062

    PubMed  Google Scholar 

  • De Meis L (1981) The sarcoplasmic reticulum. Transport and energy transduction. Wiley, New York

    Google Scholar 

  • De Meis L, Martins OB, Alves EW (1980) Role of water, hydrogen ion, and temperature on the synthesis of adenosine triphosphate by the sarcoplasmic reticulum adenosine triphosphatase in the absence of a calcium ion gradient. Biochemistry 19:4252–4261

    Article  PubMed  Google Scholar 

  • Fabiato A, Fabiato F (1979) Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol (Paris) 75:463–505

    CAS  Google Scholar 

  • Forge V, Mintz E, Guillain F (1993a) Ca2+ binding to sarcoplasmic reticulum ATPase revisited. I. Mechanism of affinity and cooperativity modulation by H+ and Mg2+. J Biol Chem 268:10953–10960

    CAS  PubMed  Google Scholar 

  • Forge V, Mintz E, Guillain F (1993b) Ca2+ binding to sarcoplasmic reticulum ATPase revisited. II. Equilibrium and kinetic evidence for a two-route mechanism. J Biol Chem 268:10961–10968

    CAS  PubMed  Google Scholar 

  • Gutierrez-Merino C, Molina A, Escudero B, Diez A, Laynez J (1989) Interaction of the local anesthetics dibucaine and tetracaine with sarcoplasmic reticulum membranes. Differential scanning calorimetry and fluorescence studies. Biochemistry 28:3398–3406

    Article  CAS  PubMed  Google Scholar 

  • Hecht JP, Nikonov JM, Alonso GL (1990) A BASIC program for the numerical solution of the transient kinetics of complex biochemical models. Comput Methods Programs Biomed 33:13–20

    Article  CAS  PubMed  Google Scholar 

  • Hill T, Inesi G (1982) Equilibrium cooperative binding of calcium and protons by sarcoplasmic reticulum ATPase. Proc Natl Acad Sci USA 79:3978–3982

    CAS  PubMed  Google Scholar 

  • Inesi G (1985) Mechanism of calcium transport. Annu Rev Physiol 47:573–601

    Article  CAS  PubMed  Google Scholar 

  • Inesi G, Lewis D, Murphy AJ (1984) Interdependence of H+, Ca2+, and Pi (or vanadate) sites in sarcoplasmic reticulum ATPase. J Biol Chem 259:996–1003

    CAS  PubMed  Google Scholar 

  • Kuroda Y, Fujiwara Y (1987) Locations and dynamical pertubations for lipids of cationic forms of procaine, tetracaine, and dibucaine in small unilamellar phosphatidylcholine vesicles as studied by nuclear Overhauser effects in 1H nuclear magnetic resonance spectroscopy. Biochim Biophys Acta 903:395–410

    CAS  PubMed  Google Scholar 

  • Lacapere JJ, Bennett N, Dupont Y, Guillan F (1990) pH and magnesium dependence of ATP binding to sarcoplasmic reticulum ATPase. Evidence that the catalytic ATP-binding site consists of two domains. J Biol Chem 255:348–353

    Google Scholar 

  • Levy D, Seigneuret M, Bluzat A, Rigaud L (1990) Evidence for proton countertransport by the sarcoplasmic reticulum Ca2+-ATPase during calcium transport in reconstituted proteoliposomes with low ionic permeability. J Biol Chem 265:19524–19534

    CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Masuda H, de Meis L (1973) Phosphorylation of the sarcoplasmic reticulum membrane by orthophosphate. Inhibition by calcium ions. Biochemistry 12:4581–4585

    Article  CAS  PubMed  Google Scholar 

  • Melzer W, Hermann-Frank A, Lüttgau HC (1995) The role of Ca2+ ions in excitation–contraction coupling of skeletal muscle fibres. Biochim Biophys Acta 1241:59–116

    CAS  PubMed  Google Scholar 

  • Ohki S (1984) Adsorption of local anesthetics on phospholipid membranes. Biochim Biophys Acta 777:56–66

    CAS  PubMed  Google Scholar 

  • Orlowski S, Lund S, Moller J, Champeil P (1988) Phosphoenzymes formed from Mg.ATP and Ca.ATP during pre-steady state kinetics of sarcoplasmic reticulum ATPase. J Biol Chem 263:17576–17583

    CAS  PubMed  Google Scholar 

  • Suko J, Winkler F, Scharinger B, Hellmann G (1976) Aspect of the mechanism of action of local anesthetics on the sarcoplasmic reticulum of skeletal muscle. Biochim Biophys Acta 441:571–586

    Google Scholar 

  • Takara D, Sánchez GA, Alonso GL (2000) Effect of carticaine on the sarcoplasmic reticulum Ca-dependent adenosine triphosphatase. Naunyn-Schmiedebergs Arch Pharmacol 362:497–503

    Article  CAS  PubMed  Google Scholar 

  • Takakuwa Y, Kanazawa T (1981) Reaction mechanism of (Ca2+, Mg2+)-ATPase of sarcoplasmic reticulum vesicles. II (ATP, ADP)-dependent Ca2+–Ca2+ exchange across the membranes. J Biol Chem 256:2696–2700

    CAS  PubMed  Google Scholar 

  • Takakuwa Y, Kanazawa T (1982) Reaction mechanism of (Ca2+, Mg2+)-ATPase of sarcoplasmic reticulum. The role of Mg2+ that activates hydrolysis of the phosphoenzyme. J Biol Chem 257:426–431

    CAS  PubMed  Google Scholar 

  • Wakabayashi S, Ogurusu T, Shigekawa M (1987) Modulation of the hydrolysis rate of the ADP-sensitive phosphoenzyme of the sarcoplasmic reticulum ATPase by H+ and Mg2+. J Biol Chem 262:9121–9129

    CAS  PubMed  Google Scholar 

  • Yamada S, Ikemoto N (1980) Reaction mechanism of calcium-ATPase of sarcoplasmic reticulum. Substrates for phosphorylation reaction and back reaction, and further resolution of phosphorylated intermediates. J Biol Chem 255:3108–3119

    CAS  PubMed  Google Scholar 

  • Yu X, Hao L, Inesi G (1994) A pk change of acidic residues contributes to cation countertransport in the Ca-ATPase of sarcoplasmic reticulum. J Biol Chem 269:16656–16661

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the Universidad de Buenos Aires, and from the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina. We are grateful to Penta Farmaceútica S.A. (Buenos Aires) and Microsules Bernabó S.A. for supplying pure carticaine chlorhydrate.

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Authors and Affiliations

  1. Cátedra de Biofísica, Facultad de Odontología, Universidad de Buenos Aires, Marcelo T. de Alvear 2142 Piso 17 B, 1122AAH, Buenos Aires, Argentina

    Delia Takara, Gabriel A. Sánchez, Augusto F. Toma, Patricia Bonazzola & Guillermo L. Alonso

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  1. Delia Takara
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  2. Gabriel A. Sánchez
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  3. Augusto F. Toma
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  4. Patricia Bonazzola
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  5. Guillermo L. Alonso
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Correspondence to Delia Takara.

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Drs. Guillermo L. Alonso and Patricia Bonazzola are established investigators of the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina

The experiments were performed in accordance with the current laws of our country

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Takara, D., Sánchez, G.A., Toma, A.F. et al. Effect of carticaine on the sarcoplasmic reticulum Ca2+-adenosine triphosphatase. II. Cations dependence. Naunyn Schmied Arch Pharmacol 371, 375–382 (2005). https://doi.org/10.1007/s00210-005-1061-7

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  • DOI: https://doi.org/10.1007/s00210-005-1061-7

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