Effect of local anesthetics on the phase transition temperatures of ether- and ester-linked phospholipid bilayer membranes

The phase-transition temperatures of ester-linked dipalmitoylphosphatidylcholine (DPPC) and ether-linked dihexadecylphosphatidylcholine (DHPC) bilayer membranes were measured as a function of the concentration of local anesthetics, dibucaine (DC.HCl), tetracaine (TC.HCl), bupivacaine (BC.HCl), lidocaine (LC.HCl) and procaine hydrochlorides (PC.HCl). The temperature of the main transition for both lipid bilayers was depressed by all the anesthetics added in a dose-dependent manner; the order of the depression of transition temperature was DC.HCl > TC.HCl > BC.HCl > LC.HCl > PC.HCl. The pretransition temperature of DPPC bilayer membrane from the lamellar gel (L'(beta)) to the ripple gel (P'(beta)) phase was depressed by the addition of local anesthetics, while the DHPC bilayer membrane undergoes the pretransition from the interdigitated gel (LbetaI) to the P'(beta) phase and the elevation of pretransition temperature was observed by the addition of local anesthetics. The presence of local anesthetics stabilize the LbetaI phase of lipid bilayer membranes. When the more hydrophobic anesthetics such as DC.HCl and TC.HCl were added sufficiently to the bilayer membrane system, the interdigitation of bilayers was induced in the DPPC membrane system and the P'(beta) phase disappeared in the DHPC membrane system. From the colligative thermodynamic framework, three kinds of differential partition coefficients corresponding to three phase-transitions, K(L-alpha)-K(P'(beta)), K(P'(beta))-K(L'(beta)) and K(P'(beta))-K(LbetaI), where K(L-alpha), K(P'(beta)), K(L'(beta)) and K(LbetaI) refer to the partition coefficients of an anesthetic into the L-alpha, P'(beta), L'(beta) and LbetaI phases of lipid bilayer membranes, were evaluated from the depression (or elevation) of the phase-transition temperature. The transfer free energy of anesthetics from the aqueous phase to the L-alpha phase of bilayers, Delta G(tr) = -RT In K(L-alpha), was well correlated to the local anesthetic potencies. (C) 2000 Elsevier Science B.V. All rights reserved.