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H Kamaya

Publications and source records attributed to H Kamaya.

At least 37 records · Page 2Linked to original sources

A statistical mechanical analysis of the effect of long-chain alcohols and high pressure upon the phase transition temperature of lipid bilayer membranes.

Long-chain n-alcohols decrease the main phase-transition temperature of lipid vesicle membranes at low concentrations but increase it at high concentrations. The nonlinear phenomenon is unrelated to the interdigitation and is analyzed by assuming that alcohols form solid solutions with solid as well as liquid phases. The biphasic response originates from the balance of the free energy difference of alcohols in the liquid and solid membranes (delta gA) and the alcohol-lipid interaction free energy difference (delta u) between the two phases. When delta gA less than 0 and delta u greater than 0, or delta gA less than delta u less than 0, the transition temperature decreases monotonously according to the increase in the alcohol concentration. When delta gA greater than 0 and delta u less than 0, or delta gA greater than delta u greater than 0, it increases monotonously. Biphasic response occurs with a minimum temperature when delta u greater than delta gA greater than 0, and with a maximum temperature when delta u less than delta gA less than 0. When the alcohol carbon-chain length becomes closer to the lipid carbon-chain length, delta u is equalized by delta gA, and the temperature minimum of the main transition is shifted to extremely low alcohol concentrations. Hence, long-chain alcohols predominantly elevate the main transition temperature and lose their anesthetic potency. High pressure decreased both delta gA and delta u. Presumably, high pressure improves the packing efficiency of liquid membranes and decreases the difference between the solid and liquid membrane properties.

Alcohols↗

Interfacial dehydration by anesthetics: an electrocapillary study of surface charge density of adsorbed monolayer.

We have proposed that anesthetics destruct the hydration shell of macromolecules irrespective of lipid membranes or proteins. These macromolecular structures are supported by the hydrogen-bonded matrix of water molecules. A loss of this support destabilizes the membranes and proteins. The disordered structures are suboptimal for the assigned biological functions, and anesthesia may ensue. We postulated that the dehydration is prompted mainly by the decrease in the interactions of the surface charges with the water dipole. To prove or disprove the above hypothesis, this study measured the effect of volatile anesthetics (chloroform, halothane, and enflurane) on the surface charge density in adsorbed monolayers by an electrocapillary method. The oil phase was methylisobutylketone (MIBK) with cetyltrimethylammonium chloride (CTAC). The aqueous phase was 0.1 M NaCl. The anesthetics decreased the surface charge density, and the effect paralleled the clinical anesthetic potency. At concentrations that induce surgical stage anesthesia in 50% of the population, these anesthetics reduced the surface charge density by 5%.

Adsorption↗

Anesthetic-protein interaction: effects of volatile anesthetics on the secondary structure of poly(L-lysine).

Effects of volatile anesthetics (chloroform, halothane, and enflurane) on the secondary structure of poly(L-lysine) were analyzed by circular dichroism (CD). The relative proportions among alpha-helix, beta-sheet, and random-coil conformations were calculated by the curve-fitting method on the CD data. Volatile anesthetics partially transformed alpha-helix to beta-sheet but not to random-coil under the present experimental condition. When expressed by the anesthetic partial pressures in the gas phase in equilibrium with the solution, the values that partially transformed alpha to beta conformation by 10% were 1.1 x 10(-2), 4.7 x 10(-2), and 7.9 x 10(-2) atm for chloroform, halothane, and enflurane, respectively. The order of potency is in reasonable agreement with the order of the anesthetic potencies of the agents. The alpha-to-beta transition was completely reversible when anesthetics were purged by nitrogen gas. Volatile anesthetics disrupted the hydrogen bonds of alpha-helix backbones and rearranged them to form the beta-sheet conformation. The beta-sheet conformation is stabilized mainly by the hydrophobic interaction among methylene side groups of poly(L-lysine). Volatile anesthetics promoted the transition by enhancing the hydrophobic interaction among side-chains and by rearranging the hydrogen bonds in the peptide backbone.

Chloroform↗

Effect of inhalation anesthetics on swimming activity of artemia salina.

The swimming movement of artemia salina in the artificial sea water was measured by using the video camera system in the absence and presence of anesthetics, i.e. enflurane, halothane, and isoflurane. The movement of artemia looked random at a glance but the obtained distribution curve for the swimming speed was skewed toward the high speed side somewhat resembling a Maxwellian distribution curve seen in the statistics of ideal gases. When anesthetic were added, the distribution curve became sharpened and shifted to the low speed side, which is similar to a behavior of ideal gases when they are cooled down. The mean swimming-speed was decreased eventually leading to an irreversible death with increasing the anesthetic dose. The activity was analyzed by using the hydrodynamic equation. The ED(50), which is a dose that causes a 50% reduction in the activity, of all anesthetics used in this study was quite similar to the MAC values for human. It was also suggested that an interaction between anesthetics and artemia was highly cooperative since the larger Hill coefficients were obtained for all three anesthetics used.

Journal Article↗

A solid-solution theory of anesthetic interaction with lipid membranes: temperature span of the main phase transition.

Anesthetics (or any other small additives) depress the temperature of the main phase transition of phospholipid bilayers. Certain anesthetics widen the temperature span of the transition, whereas others do not. The widening in a first-order phase transition is intriguing. In this report, the effects of additive molecules on the temperature and its span were explained by the solid-solution theory. By assuming coexistence of the liquid-crystal and solid-gel phases of lipid membranes at phase transition, the phase boundary is determined from the distribution of anesthetic molecules between the liquid-crystal membrane versus water and between the solid-gel membrane versus water. The theory shows that when the lipid concentration is large or when the lipid solubility of the drug is large, the width of the transition temperature increases, and vice versa. Highly lipid-soluble molecules, such as long-chain alkanols and volatile anesthetics, increase the width of the transition temperature when the lipid:water ratio is large, whereas highly water-soluble molecules, such as methanol and ethanol, do not. The aqueous phase serves as the reservoir for anesthetics. Depletion of the additive molecules from the aqueous phase is the cause of the widening. When the reservoir capacity is large, the temperature width does not increase. The theory also predicts asymmetry of the specific heat profile at the transition.

Anesthetics↗

Proton flow along lipid bilayer surfaces: effect of halothane on the lateral surface conductance and membrane hydration.

Impedance dispersion in liposomes measures the lateral charge transfer of lipid membrane surfaces. Depending on the choice of frequency between 1 kHz and 100 GHz, relaxation of the counterions at the interface, orientation of the head group, and relaxation of the bound and free water are revealed. This study measured the impedance dispersion in dipalmitoylphosphatidylcholine (DPPC) liposomes at 10 kHz. The surface conductance and capacitance showed breaks at pre- and main transition temperatures. Below the pre-transition temperature, the activation energy of the ion movement was 18.1 kJ.mol-1, which corresponded to that of the spin-lattice relaxation time of water (18.0 kJ.mol-1). At temperatures between pre- and main transition it increased to 51.3 kJ.mol-1, and agreed with 46.2-58.0 kJ.mol-1 of the activation energy of the dielectric relaxation of ice. Because the present system was salt-free, the ions were H3O+ and OH-, hence, their behavior represents that of water. The above results show that below the pre-transition temperature, the conductance is regulated by the mobility of free ions, or the number of free water molecules near the interface. On the other hand when the temperature exceeded pre-transition, melting of the surface-bound water crystals became the rate-limiting step for the proton flow. Halothane did not show any effect on the ion movement when the temperature was below pre-transition. When the temperature exceeded pre-transition, 0.35 mM halothane (equilibrium concentration) decreased the activation energy of the ion movement to 29.3 kJ.mol-1. This decrease indicates that halothane enhanced the release of the surface-bound water molecules at pre-transition. The surface-disordering effect of halothane was also shown by depression of the pre-transition temperature and decrease of the association energy among head groups from 9.7 kJ.mol-1 of the control to 5.2 kJ.mol-1 at 0.35 mM.

1,2-Dipalmitoylphosphatidylcholine↗

Anesthesia cutoff phenomenon: interfacial hydrogen bonding.

Anesthesia "cutoff" refers to the phenomenon of loss of anesthetic potency in a homologous series of alkanes and their derivatives when their sizes become too large. In this study, hydrogen bonding of 1-alkanol series (ethanol to eicosanol) to dipalmitoyl-L-alpha-phosphatidylcholine (DPPC) was studied by Fourier transform infrared spectroscopy (FTIR) in DPPC-D2O-in-CCl4 reversed micelles. The alkanols formed hydrogen bonds with the phosphate moiety of DPPC and released the DPPC-bound deuterated water, evidenced by increases in the bound O-H stretching signal of the alkanol-DPPC complex and also in the free O-D stretching band of unbound D2O. These effects increased according to the elongation of the carbon chain of 1-alkanols from ethanol (C2) to 1-decanol (C10), but suddenly almost disappeared at 1-tetradecanol (C14). Anesthetic potencies of these alkanols, estimated by the activity of brine shrimps, were linearly related to hydrogen bond-breaking activities below C10 and agreed with the FTIR data in the cutoff at C10.

1,2-Dipalmitoylphosphatidylcholine↗

Adsorption of local anesthetics on activated carbon: Freundlich adsorption isotherms.

We have shown that adsorbability of local anesthetics onto activated carbon, expressed by the partition coefficients at infinite dilution, correlated well with the pharmacological activity. However, there is no parameter that can singly express the tendency to be adsorbed. Adsorbability is a loosely defined term and its meaning varies with the adsorption model. This study showed that the logarithm of the adsorbed amount of drugs was linearly related to the logarithm of the free drug concentration, in conformity to the Freundlich adsorption isotherms. The slope of the double logarithmic plot is expressed by 1/N in the Freundlich equation and is considered to be inversely related to the drug affinity to the adsorbent. The slope was used to evaluate the tendency to be adsorbed, or "adsorbability" of seven aromatic amine local anesthetics. Phenobarbital was included to compare anionic drugs in contrast to the cationic local anesthetics. The slopes were nearly equal between the cationic and neutral local anesthetics. Apparently, the lower hydrophobicity of the cationic forms is compensated by the electrostatic attraction from the negative charges present on the activated carbon surface. With phenobarbital, the slope value of the anionic form was larger than the neutral form. The lower affinity of the anionic form may be caused by the electrostatic repulsion. The molecular size parameters (i.e., molecular weight, molar refraction, and parachor) showed a linear relationship to the slope values. It may be possible to estimate the affinity-related slope values from these parameters.

Adsorption↗

High pressure and anesthesia: compressibility, molal volume, and partial molal volume of volatile anesthetics.

This study was undertaken to provide volume data of volatile anesthetics under high pressure. Molal volumes of liquid halothane, enflurane, and isoflurane and their partial molal volumes in water and in 1-octanol were determined by high-precision solution densitometry at 25.000 +/- 0.0005 degrees C over the pressure range from ambient to 34.56 MPa (341 atm). The isothermal compressibilities of the pure anesthetics and their isothermal partial molal compressibilities at their infinite dilution in water and in 1-octanol have also been calculated at 0.1013 MPa (1 atm).

1-Octanol↗

Effect of local anesthetics on the electrical characteristics of an excitable model membrane composed of dioleyl phosphate I. Static and steady-state response.

The local anesthetics, tetracaine, procaine and lidocaine, interacted with a negatively charged lipid membrane composed of dioleyl phosphate (DOPH), which exhibited a self-sustained oscillation of the membrane potential. The anesthetics depolarized the membrane potential when present in increasing concentrations, whereas they increased the membrane resistance at low concentrations and decreased it at high concentrations. The above results were analyzed on the basis of electrochemical theory taking into account ion flux across the membrane. The electrical characteristics are affected by both the hydrophobicity and the diffusion constant of local anesthetics within the membrane.

Journal Article↗

Effect of local anesthetics on the electrical characteristics of an excitable model membrane composed of dioleyl phosphate II. Dynamic response.

The effects of local anesthetics (tetracaine, procaine and lidocaine) on self-sustained electrical oscillations were studied for a lipid membrane comprising dioleyl phosphate (DOPH). This model membrane exhibits oscillation of the membrane potential in a manner similar to that of nerve membranes, i.e., repetitive firing, in the presence of an ion-concentration gradient, on the application of d.c. electric current. Relatively weak anesthetics such as procaine and lidocaine increased the frequency of self-sustained oscillation, and finally induced aperiodic, rapid oscillation. The strong anesthetic tetracaine inhibited oscillation.

Journal Article↗

Differential affinity of charged local anesthetics to solid-gel and liquid-crystalline states of dimyristoylphosphatidic acid vesicle membranes.

Cationic local anesthetics decreased the transition temperature of the anionic phospholipid (dimyristoylphosphatidic acid, DMPA) vesicles. The counterion concentration changes the electrical double layer effect, and affects the magnitude of temperature depression caused by anesthetics. From the counterion effect on the transition-temperature depression, the partition coefficients of cationic local anesthetics to liquid-crystalline and solid-gel DMPA membranes were separately estimated. The differences in the partition coefficients between solid-gel and liquid-crystalline membranes correlated to the nerve blocking potencies. There are at least two states in the nerve membranes: resting state at higher temperature and excited state at lower temperature. We speculate that the resting state corresponds to the liquid-crystalline state, and the excited state to the solid-gel state. The difference in the partition coefficients to the resting and excited states is the cause of local anesthesia.

Anesthetics, Local↗

Changes in surface capacitance and conductance parallel to phospholipid membranes associated with phase transition: effects of halothane.

The effects of phase transition on the surface capacitance and conductance parallel to dipalmitoyl- (DPPC) and dimyristoyl-phosphatidylcholine (DMPC) membranes were studied by impedance dispersion. The phospholipid aggregates were embedded into pores of a polycarbonate filter and the impedance dispersions were measured at a frequency range from 30 Hz to 1.0 MHz. When the frequency was below 120 kHz, the capacitance showed a peak at the pretransition temperature and a steep rise at the main-transition temperature. In this system, the observed capacitance consists of frequency-dependent and -independent parts. The frequency-dependent part is a surface phenomenon and arises from the lateral motion of counterions at the membrane/water interface. The frequency-independent part represents mainly the properties of the bulk lipid phase. Addition of halothane decreased the total capacitance of the DPPC aggregates at the low frequency range to 1/2 to 1/8 of the control depending upon the temperature. The surface component was solely responsible for this capacitance decrease, because the non-surface component was slightly increased instead. The data suggest that halothane inhibited the lateral ionic flow parallel to the interface.

1,2-Dipalmitoylphosphatidylcholine↗

Saturable and unsaturable binding of a volatile anesthetic enflurane with model lipid vesicle membranes.

Presence of specific receptors for volatile anesthetics has recently been proposed (Evers, A.S. et al. (1987) Nature 328, 157-160) by a finding that halothane uptake by the rat brain was characterized, in part, by saturable binding. We report here that volatile anesthetics bind model lipid membranes also with saturable and unsaturable kinetics. Binding of enflurane to dipalmitoylphosphatidylcholine vesicle membranes was measured by gas chromatography. At low anesthetic concentrations, comparable to the clinical level, the interaction was saturable. After reaching a temporary saturation, a sudden increase in the anesthetic binding to the membrane occurred, when the anesthetic concentration in the aqueous phase exceeded 2.7 mM, or 6.3 x 10(-2) atm partial pressure in the gas phase in equilibrium with the aqueous phase. The secondary binding was linear to the aqueous anesthetic concentrations and was unsaturable to the limit of this study. We also found that enflurane self-aggregated in water above 4 mM. When the aqueous concentration exceeded 6 mM, the aggregation number was about 8. We conclude that the saturable binding indicates adsorption onto the vesicle surface, and the unsaturable binding indicates multilayer stacking of the enflurane molecules, where the initially adsorbed molecules provide the binding sites to the succeeding molecules according to the multilayer condensation kinetics. The tendency of enflurane to self-aggregate in water promotes the multilayer stacking at the surface of the membrane.

1,2-Dipalmitoylphosphatidylcholine↗

Smooth muscle contraction and local anesthetics: calmodulin-dependent myosin light-chain kinase.

Myocardial depressant action of local anesthetics at toxic concentrations is well documented. Their effect on vascular smooth muscle, however, remains controversial. This study analyzed local anesthetic action on the subcellular smooth-muscle contractile system. Highly purified smooth-muscle myosin and myosin light-chain kinase (MLCK) were prepared from fresh turkey gizzards, and the phosphorylation of the myosin light-chain in the presence of Ca++ and calmodulin was evaluated by the urea gel-electrophoresis. Tetracaine 1.3.10(-3) M and bupivacaine 7.5.10(-3) M inhibited the MLCK 50%, whereas lidocaine 2.5.10(-2) M inhibited the MLCK 40%. The inhibitory action was partially reversed by increasing the calcium ion concentration from 1.10(-5) to 2.10(-4) M. On the other hand, raising the calmodulin concentration from 1.10(-7) M to 6.10(-7) M completely reversed the inhibition. A possible cause of the discrepancy in the anesthetic concentrations between subcellular and in vivo studies is discussed.

Bupivacaine↗

Depression of phase-transition temperature by anesthetics: nonzero solid membrane binding.

The anesthetic-induced depression of the main phase-transition temperature of phospholipid membranes is often analyzed according to the van't Hoff model on the freezing point depression. In this procedure, zero interaction between anesthetics and solid-gel membranes is assumed. Nevertheless, anesthetics bind to solid-gel membranes to a significant degree. It is necessary to analyze the difference in the anesthetic binding between the liquid-crystal and solid-gel membranes to probe the anesthetic action on the lipid membranes. This article describes a theory to estimate the anesthetic binding to each state at the phase-transition temperature. The equations derived here reveal the relation between the partition coefficients of anesthetics and the anesthetic effects on the transition characters: the change in the transition temperature, and the broadening of transition. The theory revealed that the width of transition temperature is determined primarily by the membrane/buffer partition coefficients of anesthetics. Our previous data on the local anesthetic action on the transition temperature of the dipalmitoylphosphatidylcholine vesicle membrane (Ueda, I., Tashiro, C. and Arakawa, K. (1977) Anesthesiology 46, 327-332) are analyzed by this method. The numerical values for the partition of local anesthetics into the liquid-crystal and solid-gel dipalmitoyl-phosphatidylcholine vesicle membranes at the phase-transition temperature are: procaine 8.0 x 10(3) and 4.7 x 10(3), lidocaine, 3.7 x 10(3) and 2.3 x 10(3), bupivacaine 4.1 x 10(4), and 2.6 x 10(4), and tetracaine 7.3 x 10(4) and 4.7 x 10(4), respectively.

1,2-Dipalmitoylphosphatidylcholine↗

Effect of surface ionization of dimyristoylphosphatidic acid vesicle membranes on the main phase-transition enthalpy and temperature.

The main phase transition of phospholipid bilayers is a property expressed by the order-disorder conformational change of the lipid tails. Nevertheless, with ionizable phospholipids, changes in the surface charge have large effects on the membrane properties. The free energy of a charged phospholipid membrane depends on the degree of ionization, area per phospholipid molecule, and the temperature. Here, the effect of surface electrostatic charges on the temperature and the enthalpy of the main phase transition of dimyristoylphosphatidic acid vesicle membranes is analyzed. A simple equation is presented that describes the relationship among the surface charge density, the phase-transition temperature, the surface area ratio between solid and liquid membranes, and the excess enthalpy. The theory indicated that the pH-induced shift in the excess enthalpy is attributable to the change in the surface area ratio between the solid and liquid membranes.

Calorimetry, Differential Scanning↗