Interactions of the local anesthetic tetracaine with glyceroglycolipid bilayers: a 2H-NMR study.

We have examined the effects of the local anesthetic tetracaine on the orientational and dynamic properties of glycolipid model membranes. We elected to study the interactions of tetracaine with the pure glycolipid 1,2-di-O-tetradecyl-3-O-(beta-D-glucopyranosyl)-sn-glycerol (beta-DTGL) and a mixture of beta-DTGL (20 mol%) in dimyristoylphosphatidylcholine (DMPC) by deuterium NMR (2H-NMR) spectroscopy. 2H-NMR spectra of beta-DTGL have been measured as a function of temperature in the presence of both the charged (pH 5.5) and uncharged forms (pH 9.5) of tetracaine. The results indicate that the anesthetic induces the formation of non-lamellar phases. Specifically, the incorporation of uncharged tetracaine results in the formation of a hexagonal phase which is stable from 52 to 60 degrees C. At lower pH, the spectrum at 52 degrees C is very reminescent of that of the beta-glucolipid alone in a bilayer environment, while as the temperature is elevated to 60 degrees C, a transition from a spectrum indicative of axial symmetry to one due to nearly isotropic motion or symmetry occurs, which may result from the formation of a cubic phase. Although it leads to an alteration in the phase behavior, the presence of tetracaine does not induce large changes in the headgroup orientation of beta-DTGL. In contrast to the pure glycolipid situation, the interaction of tetracaine with beta-DTGL (20 mol%) in DMPC does not trigger the formation of non-lamellar phases, but leads to a slight reduction in molecular ordering. The presence of the charged form of the local anesthetic near the aqueous interface of the bilayer appears to induce a small change in the conformation about the C2-C3 bond of the glycerol backbone of beta-DTGL in the mixed lipid system. Thus, the major influence of the local anesthetic on glycolipids is a change in the stability of the lamellar phase, facilitating conversion to phases with hexagonal or isotropic environments for the lipid molecules.