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 reg ions of the bilayer. Parathion disorders the gel phase of liposomes re constituted with dimyristoylphosphatidylcholine (DMPC), broadening the transition profile and shifting the temperature midpoint of the phase transition, as detected by both probes. The insecticide strongly orde rs the fluid phase either in the hydrophobic core or in the outer regi ons of the membrane, as evaluated by DPH and DPH-PA, respectively. The se ordering effects of parathion were further confirmed in fluid model s of egg-yolk phosphatidylcholine. Parathion increases to some extent the ordering promoted by cholesterol in DMPC bilayers, but high choles terol concentrations (greater than or equal to 130 mol%) prevent parat hion interaction. The results in native membranes correlate reasonably with those obtained in models of synthetic lipids. Thus, parathion do es 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 cont ent of cholesterol. Again, in agreement with the models of synthetic l ipids, pronounced ordering effects of parathion are detected in choles terol-poor membranes, e.g., sarcoplasmic reticulum and mitochondria.