Advertisement

Interaction of Amphiphilic Molecules with Biological Membranes

A Model for Nonspecific and Specific Drug Effects with Membranes
  • L. Herbette
  • C. A. Napolitano
  • F. C. Messineo
  • A. M. Katz
Part of the Advances in Myocardiology book series (ADMY)

Abstract

The nonspecific interactions of propranolol, timolol, and ethanol with model and sarcoplasmic reticulum membranes were determined utilizing radioisotopic association, differential scanning calorimetry, and neutron diffraction. Differential scanning calorimetry performed on mixtures of these amphiphilic compounds and model membrane bilayers composed of dimyristoyllecithin showed that propranolol was approximately 25 times more lipid-soluble than timolol and at least 100 times more lipid-soluble than ethanol. Neutron diffraction showed that the solvation of propranolol was within the fatty acyl chain region of the lipid bilayer. This solvation correlated with the effect of propranolol to inhibit ATP-dependent calcium transport in isolated rabbit skeletal muscle sarcoplasmic reticulum, a membrane that lacks β-adrenergic receptors. In contrast, the major site of interaction of ethanol was within the aqueous compartment hydrating the sarcoplasmic reticulum membrane. A model for nonspecific drug interaction with the sarcoplasmic reticulum membrane based on the site of interaction of these amphiphiles and their relative potencies to inhibit calcium transport by these membranes is proposed. In principle, this model could be extended to specific drug interactions with membranes.

Keywords

Partition Coefficient Lipid Bilayer Sarcoplasmic Reticulum Neutron Diffraction Calcium Transport 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Seeman, P. 1972. The membrane actions of anesthetics and tranquilizers. Pharmacol. Rev. 24:583–655.PubMedGoogle Scholar
  2. 2.
    Katz, A. M., and Messineo, F. C. 1981. Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ. Res. 48:1–16.PubMedCrossRefGoogle Scholar
  3. 3.
    Herbette, L., Messineo, F. C., and Katz, A. M. 1981. The interaction of drugs with the sarcoplasmic reticulum. Annu. Rev. Pharmacol. Toxicol. 22:413–434.CrossRefGoogle Scholar
  4. 4.
    Moules, I. K., Rooney, E. K., and Lee, A. G. 1982. Binding of amphipathic drugs and probes to biological membranes. FEBS Lett. 138:95–100.PubMedCrossRefGoogle Scholar
  5. 5.
    Conrad, M. J., and Singer, S. J. 1981. The solubility of amphipathic molecules in biological membranes and lipid bilayers and its implications for membrane structure. Biochemistry 20:807–818.CrossRefGoogle Scholar
  6. 6.
    Katz, A. M., Repke, D. I., and Hassalback, W. 1977. Dependence of ionophore and caffeine-induced calcium release from sarcoplasmic reticulum vesicles on external and internal calcium ion concentrations. J. Biol. Chem. 252:1938–1949.PubMedGoogle Scholar
  7. 7.
    Herbette, L., Katz, A. M., and Sturtevant, J. M. 1983. Comparisons of the interaction of propranolol and timolol with model and biological membrane systems. Mol. Pharmacol. 24:259–269.PubMedGoogle Scholar
  8. 8.
    Scarpa, A. 1979. Measurement of calcium ion concentrations with metallochromic indicators. In: Detection and Measurement of Free Calcium in Cells. C. Ashley and A. Campbell (eds.), pp. 85–115, Elsevier, Amsterdam.Google Scholar
  9. 9.
    Herbette, L., Marquardt, J., Scarpa, A., and Blasie, J. K. 1977. A direct analysis of lamellar x-ray diffraction from hydrated oriented multilayers of fully functional sarcoplasmic reticulum. Biophys. J. 20:245–272.PubMedCrossRefGoogle Scholar
  10. 10.
    Messineo, F. C., and Katz, A. M. 1979. Effects of propranolol and timolol on calcium uptake by sarcoplasmic reticulum vesicles. J. Cardiovasc. Pharmacol. 1:449–459.PubMedCrossRefGoogle Scholar
  11. 11.
    Privalov, P. L., Plotniko, V. V., and Filimono, V. V. 1975. Precision scanning microcalorimeter for study of liquids. J. Chem. Thermodynam. 7:41–47.CrossRefGoogle Scholar
  12. 12.
    Herbette, L., Wang, C. T., Saito, A., Fleischer, S., Scarpa, A., and Blasie, J. K. 1981. A comparison of the profile structures of isolated and reconstituted sarcoplasmic reticulum membranes. Biophys. J. 36:47–72.PubMedCrossRefGoogle Scholar
  13. 13.
    Schoenborn, B. P., and Nunes, A. C. 1972. Neutron scattering. Annu. Rev. Biophys. Bioeng. 1:529–552.PubMedCrossRefGoogle Scholar
  14. 14.
    Herbette, L., Scarpa, A., Blasie, J. K., Wang, C. T., Hymel, L., Seelig, J., and Fleischer, S. 1983. The determination of the separate Ca2+ pump protein and phospholipid profile structures within reconstituted sarcoplasmic reticulum membranes via x-ray and neutron diffraction. Biochim. Biophys. Acta 730:369–378.PubMedCrossRefGoogle Scholar
  15. 15.
    Lowry, O. H., Rosenbrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with Folin reagent. J. Biol. Chem. 193:265–275.PubMedGoogle Scholar
  16. 16.
    Chen, P. S., Toribara, T. B., and Warner, H. 1956. Microdetermination of phosphorus. Anal. Chem. 28 :1756–1758 .CrossRefGoogle Scholar
  17. 17.
    Hill, M. W. 1974 The effect of anesthetic-like molecules on the phase transition in smectic mesophases of dipalmitoyllecithin. I. The normal alcohol up to C= 9 and three inhalation anesthetics. Biochim. Biophys. Acta 356:117–124.PubMedCrossRefGoogle Scholar
  18. 18.
    Buldt, G., Gally, H. U., Seelig, J., and Zaccai, G. 1979. Neutron diffraction studies on phosphatidylcholine model membranes. I. Head group conformation. J. Mol. Biol. 134:673–691.PubMedCrossRefGoogle Scholar
  19. 19.
    Davis, D. G., Inesi, G., and Gulik-Krzywicki, T. 1976. Lipid molecular motion and enzyme activity in sarcoplasmic reticulum membrane. Biochemistry 15:1271–1276.PubMedCrossRefGoogle Scholar
  20. 20.
    Vanderkooi, J. M., Landesberg, R., Selick, H., and Mc Donald, G. G. 1977. Interaction of general anesthetics with phospholipid vesicles and biological membranes. Biochim. Biophys. Acta 464:1–16.PubMedCrossRefGoogle Scholar
  21. 21.
    Pringle, M. J., Brown, K. B., and Miller, K. W. 1981. Can the lipid theories of anesthesia account for the cutoff in anesthetic potency in homologous series of alcohols? Mol. Pharmacol. 19:49–55.PubMedGoogle Scholar
  22. 22.
    Katz, Y., and Diamond, J. M. 1974. Thermodynamic constants for nonelectrolyte partition between dimyristoyl lecithin and water. J. Membrane Biol. 17:101–120.CrossRefGoogle Scholar
  23. 23.
    Katz, A. M., Nash-Adler, P., Watras, J., Messineo, F. C., Takenaka, H., and Louis, C. F. 1982. Fatty acid effects on calcium influx and efflux in sarcoplasmic reticulum vesicles from rabbit skeletal muscle. Biochim. Biophys. Acta 687:17–26.PubMedCrossRefGoogle Scholar
  24. 24.
    Herbette, L. G., Sarmiento, J. G., and Rhodes, D. G. 1984. Mechanism for cardiovascular drug binding to membrane associated receptors: Approach to the binding site through the lipid bilayer. Biophys. J. 45:312a.Google Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • L. Herbette
    • 1
  • C. A. Napolitano
    • 2
  • F. C. Messineo
    • 2
  • A. M. Katz
    • 2
  1. 1.Departments of Medicine and BiochemistryUniversity of Connecticut Health CenterFarmingtonUSA
  2. 2.Department of MedicineUniversity of Connecticut Health CenterFarmingtonUSA

Personalised recommendations