Effects of parathion on membrane organization and its implications for the mechanisms of toxicity

The effects of the organophosphorus insecticide parathion (O,O-diethyl O-(p-nitrophenyl)phosphorothioate) on the physical state of synthetic and native membranes was investigated by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), probing the bilayer core, and by its anionic propionic acid derivative (DPH-PA), probing the outer regions of the bilayer. Parathion disorders the gel phase of liposomes reconstituted with dimyristoylphosphatidylcholine (DMPC), broadening the transition profile and shifting the temperature midpoint of the phase transition, as detected by both probes. The insecticide strongly orders the fluid phase either in the hydrophobic core or in the outer regions of the membrane, as evaluated by DPH and DPH-PA, respectively. These ordering effects of parathion were further confirmed in fluid models of egg-yolk phosphatidylcholine. Parathion increases to some extent the ordering promoted by cholesterol in DMPC bilayers, but high cholesterol concentrations (> or = 30 mol%) prevent parathion interaction. The results in native membranes correlate reasonably with those obtained in models of synthetic lipids. Thus, parathion does not exert detectable effects in cholesterol-rich membranes, namely, erythrocytes, but moderate ordering effects of parathion are detected by both probes in brain microsomes, i.e., membranes with a lower content of cholesterol. Again, in agreement with the models of synthetic lipids, pronounced ordering effects of parathion are detected in cholesterol-poor membranes, e.g., sarcoplasmic reticulum and mitochondria.