FLUORESCENT STUDIES ON THE INTERACTION BETWEEN A NOVEL CA-2+ ANTAGONIST, SR-33557, AND MEMBRANE-LIPIDS

The fluorescent properties of SR 33557, a novel calcium entry blocker, have been characterized in solution and when interacting with phospholipid vesicles and natural membranes. The intensity and lifetime of fluorescence emission increased directly as a function of the decrease in the solvent dielectric constant (epsilon) with no change in the emission wavelength maxima. The quantum yield and the fluorescence lifetime in dioxane were 0.90 and 11.1 nsec, respectively. In various vesicles and in erythrocyte ghosts, SR 33557 was shown to be located in a lipidic environment corresponding to an epsilon of 30 congruent-to 40. At 25-degrees, the dissociation constant (K(d)) was 1.1-7.3 x 10(-6) M with a maximum of 15 SR 33557 molecules bound per 100 phospholipid molecules. When interacting with phospholipids, SR 33557 exhibited two fluorescence lifetimes (approximately 13 and 4 nsec) with the fractional contribution of 81 and 19% of the total decay, respectively. Binding of SR 33557 was enthalpy-driven. Both intensity of fluorescence emission and of fluorescence polarization of SR 33557 were indices of phase transitions in phospholipid vesicles. Thus, SR 33557 has fluorescent properties which may be of use in the study of its mode of action in biological media.