Effect of local anesthetics on the bilayer membrane of dipalmitoylphosphatidylcholine: interdigitation of lipid bilayer and vesicle-micelle transition

The phase transitions of dipalmitoylphosphatidylcholine (DPPC) bilayer memb rane were observed by means of differential scanning calorimetry (DSC) as a function of the concentration of local anesthetics, dibucaine (DC.HCl), te tracaine (TC.HCl), lidocaine (LC.HCl) and procaine hydrochlorides (PC.HCl). LC.HCl and PC.HCl depressed monotonously the temperatures of the main- and pre-transition of DPPC bilayer membrane. The enthalpy changes of both tran sitions decreased slightly with an increase in anesthetic concentration up to 160 mmol kg(-1). In contrast, the addition of TC.HCl or DC.HCl, having t he ability to form a micelle by itself, induced the complex phase behavior of DPPC bilayer membrane including the vesicle-to-micelle transition. The d epression of both temperatures of the main- and pre-transition, which is ac companied with a decrease in enthalpy, was observed by the addition of TC.H Cl up to 21 mmol kg(-1) or DC.HCl up to 11 mmol kg(-1). The pretransition d isappeared when these concentrations of anesthetic were added, and the inte rdigitated gel phase appeared above these concentrations. The appearance of the interdigitated gel phase, instead of the ripple gel phase, brings abou t the stabilization of the gel phase by 1.8-2.4 kcal mol(-1). In the concen tration range of 70-120 mmol kg(-1) TC.HCl (or 40-60 mmol kg(-1) DC.HCl), t he 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, resu lting in the mixed micelle of DPPC and anesthetics. Therefore, in this rang e of anesthetic concentration, the DPPC vesicle solubilized an anesthetic w hich coexists with the DPPC-anesthetic mixed micelle. Above the concentrati on of 120 mmol kg(-1) TC.HCl (or 60 mmol kg(-1) DC.HCl), there exists the D PPC-anesthetic mixed micelle. Two types of new transitions concerned with t he mixed micelle of DPPC and micelle-forming anesthetics were observed by D SC. (C) 2000 Elsevier Science B.V. All rights reserved.