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Local anesthetic-divalent cation binding center interaction.

C Gutiérrez-Merino1, P Macias

  • 1Departamento de Bioquímica y Biología Molecular y Genètica, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.

Biochemical Pharmacology
|May 1, 1989
PubMed
Summary
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Local anesthetics interact with divalent cation binding sites, influencing their fluorescence spectra. This suggests a strong binding potential to calcium and magnesium centers, crucial for understanding anesthetic receptor sites.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Physical Chemistry

Background:

  • Local anesthetics are known to interact with biological membranes.
  • Divalent cations play crucial roles in various biological processes.
  • Understanding the physical-chemical interactions of local anesthetics is key to defining their receptor sites.

Purpose of the Study:

  • To investigate the interaction between local anesthetics and divalent cation binding centers.
  • To elucidate the mechanism of interaction using spectrofluorometric methods.
  • To estimate the binding affinity and thermodynamic parameters of these interactions.

Main Methods:

  • Spectrofluorometry was employed to study the fluorescence changes of local anesthetics and chelators.
  • Experiments were conducted in the presence of ethyleneglycol bis (B-aminoethyl ether)-N-N,N',N'-tetraacetic acid (EGTA), ethylenediamine tetraacetic acid (EDTA), and ATP.

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  • Association constants were determined to calculate the free energy of interaction.

    • Main Results:

    • Local anesthetics altered the fluorescence spectra of EGTA, EDTA, and ATP.
    • Local anesthetics enhanced the fluorescence of chlortetracycline and quenched the fluorescence of quin 2.
    • The observed fluorescence changes were attributed to quantum yield variations, indicating direct interaction.
    • Estimated free energy of interaction ranged from -2.8 to -4.0 kcal/mole at pH 7.4 and 0.1 ionic strength at 25°C.

    Conclusions:

    • Local anesthetics interact with divalent cation binding centers in solution.
    • The interaction likely involves the electron-deficient aromatic ring of local anesthetics with M2+ binding sites.
    • Local anesthetics exhibit strong binding potential to Ca2+ and Mg2+ binding centers when a hydrophobic region is present.