Nerve cell excitation is probably a function assigned to membrane proteins embedded into lipid bilayers. Despite the general contention that the final target of anesthetic actions may be proteins, the effect is often considered to be secondary to the change in the solvent property of supporting lipid bilayers. Nevertheless, there is evidence of direct protein-anesthetic interaction. Probably the most conclusive is the inhibition of lipid-free light emitting enzymes by inhalation anesthetics. We propose that actions of inhalation anesthetics are directed to macro-molecule-water interfaces, affecting lipids and proteins indiscriminately. This project aims at elucidation of direct interactions between proteins and inhalation anesthetics. anesthetic interactions with lipid membranes will be investigated in a separate project. Macromolecular structure, regardless of whether they are proteins or lipid membranes, are supported by interaction forces between macromolecules and the hydrogen-bonded matrix of water molecules. Anything that weakens this interaction induces disorder in the macromolecular structure. We hypothesize that the primary action of anesthetics is to weaken macromolecule-water interaction. In this context, anesthetics are not a membrane stabilizer but a destabilizer. To provide or disprove this hypothesis, anesthetic effects upon interfacial properties of macromolecules are examined. Our previous project was mainly composed of model macromolecules. There is an obvious need to compare the change in physical properties with protein functions. For this reason, we include light emitting enzymes, where functions can be conveniently analyzed by measuring the light intensity. Methods of estimating macro-melecular physical properties consist of standard colloid and interface chemistry procedures that have been successfully used in previous funding periods.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Utah
Schools of Medicine
Salt Lake City
United States
Zip Code
Abe, I; Kamaya, H; Ueda, I (1990) Adsorption of local anesthetics on activated carbon: Freundlich adsorption isotherms. J Pharm Sci 79:354-8
Yoshida, T; Okabayashi, H; Kamaya, H et al. (1989) Saturable and unsaturable binding of a volatile anesthetic enflurane with model lipid vesicle membranes. Biochim Biophys Acta 979:287-93
Kaminoh, Y; Inoue, T; Ma, S M et al. (1988) Membrane-buffer partition coefficients of tetracaine for liquid-crystal and solid-gel membranes estimated by direct ultraviolet spectrophotometry. Biochim Biophys Acta 946:337-44
Kaminoh, Y; Tashiro, C; Kamaya, H et al. (1988) Depression of phase-transition temperature by anesthetics: nonzero solid membrane binding. Biochim Biophys Acta 946:215-20
Abe, I; Kamaya, H; Ueda, I (1988) Activated carbon as a biological model: comparison between activated carbon adsorption and oil-water partition coefficient for drug activity correlation. J Pharm Sci 77:166-8
Nosaka, S; Kamaya, H; Ueda, I (1988) High pressure and anesthesia: pressure stimulates or inhibits bacterial bioluminescence depending upon temperature. Anesth Analg 67:988-92
Kaminoh, Y; Kano, F; Chiou, J S et al. (1988) Effect of surface ionization of dimyristoylphosphatidic acid vesicle membranes on the main phase-transition enthalpy and temperature. Biochim Biophys Acta 943:522-30
Tsai, Y S; Ma, S M; Kamaya, H et al. (1987) Fourier transform infrared studies on phospholipid hydration: phosphate-oriented hydrogen bonding and its attenuation by volatile anesthetics. Mol Pharmacol 31:623-30
Suezaki, Y; Shirahama, K; Ohshima, H et al. (1987) Origin of calcium-induced minimum in bulk compressional modulus of lipid membranes. Configurational entropy of adsorbed Ca2+. Biophys Chem 28:13-9
Mashimo, T; Kamaya, H; Ueda, I (1986) Anesthetic-protein interaction: surface potential of bovine serum albumin estimated by a pH-sensitive dye. Mol Pharmacol 29:149-54

Showing the most recent 10 out of 20 publications