EFFECTS OF METHYLPARATHION ON MEMBRANE FLUIDITY AND ITS IMPLICATIONS FOR THE MECHANISMS OF TOXICITY

As probed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatrien e (DPH) and 3-[p-(6-phenyl)-1,3,5-hexatrienyl] phenylpropionic acid (D PH-PA), methylparathion decreases the phase transition midpoint of dim yristoylphosphatidylcholine (DMPC) bilayers and broadens the transitio n profile. Furthermore, the insecticide orders to some extent the flui d phase of DMPC, in either the hydrophobic core or in the outer region s of the membrane, as evaluated by DPH and DPH-PA, respectively. These condensing effects of methylparathion were further confirmed in fluid models of egg-yolk phosphatidylcholine. The insecticide increases to some extent the ordering promoted by cholesterol in fluid bilayers of DMPC, but high cholesterol concentrations (greater than or equal to 30 mol%) prevent methylparathion interaction. In agreement with the data in models of synthetic lipids, the condensing effects of methylparath ion in fluid native membranes of mitochondria, sarcoplasmic reticulum and erythrocytes are depressed with the increase in intrinsic choleste rol. Therefore, the effects of methylparathion are modulated, to a gre at extent, by membrane cholesterol concentration. Consequently, it can be suggested that the fluidity effects of methylparathion would be pr eferentially exerted in biomembranes scarce in cholesterol, e.g. mitoc hondria and sarcoplasmic reticulum. The perturbations promoted by meth ylparathion in these highly functional membranes will certainly induce bioenergetic alterations endangering cell and tissue functions, since membrane fluidity is a crucial parameter in the control of basic memb rane mechanisms and, consequently, in cell homoeostasis. (C) 1997 Else vier Science Ltd.