Hata T, Matsuki H, Kaneshina S
Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, Minamijosanjima, Japan.
Biophys Chem. 2000 Sep 15;87(1):25-36. doi: 10.1016/s0301-4622(00)00175-7.
The phase transitions of dipalmitoylphosphatidylcholine (DPPC) bilayer membrane were observed by means of differential scanning calorimetry (DSC) as a function of the concentration of local anesthetics, dibucaine (DC x HCl), tetracaine (TC x HCl), lidocaine (LC x HCl) and procaine hydrochlorides (PC x HCl). LC x HCl and PC x HCl depressed monotonously the temperatures of the main- and pre-transition of DPPC bilayer membrane. The enthalpy changes of both transitions decreased slightly with an increase in anesthetic concentration up to 160 mmol kg(-1). In contrast, the addition of TC x HCl or DC x HCl, having the ability to form a micelle by itself, induced the complex phase behavior of DPPC bilayer membrane including the vesicle-to-micelle transition. The depression of both temperatures of the main- and pre-transition, which is accompanied with a decrease in enthalpy, was observed by the addition of TC x HCl up to 21 mmol kg(-1) or DC x HCl up to 11 mmol kg(-1). The pretransition disappeared when these concentrations of anesthetic were added, and the interdigitated gel phase appeared above these concentrations. The appearance of the interdigitated gel phase, instead of the ripple gel phase, brings about the stabilization of the gel phase by 1.8-2.4 kcal mol(-1). In the concentration range of 70-120 mmol kg(-1) TC x HCl (or 40-60 mmol kg(-1) DC x HCl), the enthalpy of the main transition exhibited a drastic decrease, resulting in the virtual disappearance of the main transition. This process includes the decrease in vesicle size with increasing anesthetic concentration, resulting in the mixed micelle of DPPC and anesthetics. Therefore, in this range of anesthetic concentration, the DPPC vesicle solubilized an anesthetic which coexists with the DPPC-anesthetic mixed micelle. Above the concentration of 120 mmol kg(-1) TC x HCl (or 60 mmol kg(-1) DC x HCl), there exists the DPPC-anesthetic mixed micelle. Two types of new transitions concerned with the mixed micelle of DPPC and micelle-forming anesthetics were observed by DSC.
通过差示扫描量热法（DSC）观察了二棕榈酰磷脂酰胆碱（DPPC）双层膜的相变，该相变是作为局部麻醉剂丁卡因（DC x HCl）、丁哌卡因（TC x HCl）、利多卡因（LC x HCl）和盐酸普鲁卡因（PC x HCl）浓度的函数。LC x HCl和PC x HCl单调降低DPPC双层膜主转变和预转变的温度。随着麻醉剂浓度增加至160 mmol kg⁻¹，两种转变的焓变略有下降。相比之下，自身具有形成胶束能力的TC x HCl或DC x HCl的加入，诱导了DPPC双层膜复杂的相行为，包括囊泡到胶束的转变。加入高达21 mmol kg⁻¹的TC x HCl或高达11 mmol kg⁻¹的DC x HCl时，观察到主转变和预转变的温度均降低，同时焓也降低。当加入这些浓度的麻醉剂时，预转变消失，并且在这些浓度以上出现了交叉排列的凝胶相。交叉排列的凝胶相而非波纹凝胶相的出现，使凝胶相稳定了1.8 - 2.4 kcal mol⁻¹。在70 - 120 mmol kg⁻¹的TC x HCl（或40 - 60 mmol kg⁻¹的DC x HCl）浓度范围内，主转变的焓急剧下降，导致主转变几乎消失。这个过程包括随着麻醉剂浓度增加囊泡尺寸减小，从而形成DPPC与麻醉剂的混合胶束。因此，在这个麻醉剂浓度范围内，DPPC囊泡溶解了与DPPC - 麻醉剂混合胶束共存的麻醉剂。在高于120 mmol kg⁻¹的TC x HCl（或60 mmol kg⁻¹的DC x HCl）浓度时，存在DPPC - 麻醉剂混合胶束。通过DSC观察到了与DPPC和形成胶束的麻醉剂的混合胶束相关的两种新型转变。
