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Interaction of Amphiphilic Molecules with Biological Membranes

A Model for Nonspecific and Specific Drug Effects with Membranes

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Advances in Myocardiology

Part of the book series: Advances in Myocardiology ((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.

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Authors and Affiliations

  1. Departments of Medicine and Biochemistry, University of Connecticut Health Center, Farmington, Connecticut, 06032, USA

    L. Herbette

  2. Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut, 06032, USA

    C. A. Napolitano, F. C. Messineo & A. M. Katz

Authors
  1. L. Herbette
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  2. C. A. Napolitano
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  3. F. C. Messineo
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  4. A. M. Katz
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Editor information

Editors and Affiliations

  1. Cardiothoracic Institute, University of London, London, England

    Peter Harris  & Philip A. Poole-Wilson  & 

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© 1985 Springer Science+Business Media New York

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Herbette, L., Napolitano, C.A., Messineo, F.C., Katz, A.M. (1985). Interaction of Amphiphilic Molecules with Biological Membranes. In: Harris, P., Poole-Wilson, P.A. (eds) Advances in Myocardiology. Advances in Myocardiology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1287-2_25

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  • DOI: https://doi.org/10.1007/978-1-4757-1287-2_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1289-6

  • Online ISBN: 978-1-4757-1287-2

  • eBook Packages: Springer Book Archive

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