title: Organic solvents increase membrane fluidity and affect bile flow and K+ transport in rat liver.
abstract: Following the earlier observation that inhalation of volatile lipid solvents and of narcotic gases causes cholestasis, we studied the effects of various organic solvents on bile flow, plasma membrane fluidity and potassium movement in rat liver. Both in vivo and in the isolated perfused liver, applications of CCl4, CHCl3, dichloromethane, trichloroethylene, halothane, benzene and cyclohexane elicited rapid and sustained but reversible cholestasis. A transient phase of choleresis was observed prior to and after cholestasis, during the increase and fall in liver tissue solvent concentrations, respectively. Tissue concentrations required to produce cholestasis were lower the higher the lipophilicity of the solvent. Membrane fluidity was measured in isolated basolateral liver cell membranes by fluorescence polarization. Fluidity increased with increasing solvent concentration, the increase being associated with either biphasic stimulation and inhibition of membrane enzymes (Na+,K(+)-ATPase, 5'nucleotidase) or with inhibition alone (Mg(2+)-ATPase). In the isolated perfused liver, application of organic solvents caused hepatic uptake of K+ that was followed by K+ release upon withdrawal of the solvent. The magnitude of K+ uptake elicited by the solvent was comparable with the effect of blocking K+ channels with 2 mM Ba2+, but Ba2+ was ineffective in the presence of the solvent. In contrast, application of ouabain caused K+ release in equal amounts in the absence and presence of the solvent, indicating that K+ uptake elicited by the solvent results from inhibition of K+ efflux through K+ channels rather than stimulation of the Na+,K+ pump. The data show that cholestasis elicited by lipid solvents is associated with an increase in membrane fluidity and with disturbance of liver K+ homeostasis. The significance of these observations is discussed with respect to other models of experimental cholestasis.
authors.affiliation: Department of General and Experimental Pathology, University of Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Thalhammer
authors.forename: R
authors.initials: R
authors.lastname: Kaschnitz
authors.forename: K
authors.initials: K
authors.lastname: Mittermayer
authors.forename: P
authors.initials: P
authors.lastname: Haddad
authors.forename: J
authors.initials: J
authors.lastname: Graf
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology; D001646:Bile / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D012997:Solvents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D008563:Membrane Lipids; D015221:Potassium Channels; D012997:Solvents; D001464:Barium; D010042:Ouabain