SALICYLIC-ACID INDUCES CHANGES IN THE PHYSICAL-PROPERTIES OF MODEL AND NATIVE KIDNEY MEMBRANES

Salicylic acid (SA) can inhibit the facilitated transport of inorganic sulfate in the kidney, placenta, and erythrocytes. One mechanism of t his inhibition could involve the interaction of SA with membranes, res ulting in altered function of transporter protein(s) due to changes in membrane fluidity. Such membrane effects could result in altered memb rane transport and consequently in changes in the pharmacokinetics and the therapeutic activity of bath xenobiotics and endogenous substrate s. We investigated the effect of SA on the fluidity of brush border me mbrane (BBM) and basolateral membrane (BLM) isolated from rat kidney a nd also on the physical properties (such as phase transition temperatu re and fluidity) of model membranes by fluorescence polarization and d ifferential scanning calorimetry (DSC) techniques. SA decreased the li pid order parameter (S) of BBM and BLM membranes in a concentration-de pendent manner, indicating that the addition of SA makes the membrane more fluid. The fluidizing effect of SA was more pronounced than that of benzyl alcohol. Studies were carried out with protein-free model me mbranes composed of dipalmitoylphosphatidylcholine (DPPC) to investiga te the effects of SA on the bilayer membrane lipids. SA decreased the fluorescence polarization of DPH (1,6-diphenyl 1,3,5-hexatriene) incor porated in DPPC vesicles. DSC studies demonstrated that SA broadened t he phase transition temperature df DPPC vesicles and suggested that SA is located in the C-1-C-8 region of the acyl chain. In protein-free m odel membranes, SA exerted fluidizing effects through its incorporatio n into the cooperative hydrophobic region of the bilayer. The perturba tion of membrane physical properties induced by SA and its hydrophobic localization in the membrane bilayer may be important in the SA-induc ed alteration of sulfate membrane transport.