Membrane fluidity and bile salt damage.
The lysis, by bile salts, of membranes of different fluidities was studied; it was shown that membranes of low fluidity were less readily lysed than membranes of higher fluidity. Membrane fluidity levels were controlled (i) by the use of erythrocytes, from different species, systematically differing in their lipid composition; (ii) by using each membrane at a range of temperatures; and (iii) by incorporating into the membranes the fluidizing agent, benzyl alcohol, at a range of concentrations. Membrane fluidity (and order) in each case was monitored by measuring the degree of polarization of fluorescence from the hydrophobic probe molecule, 1,6-diphenyl-1,3,5-hexatriene. The response of lytic behaviour to modulations of membrane fluidity also indicated a difference between the bile salts, glycodeoxycholate and glycocholate; the former initiates lysis close to (at or below) its critical micellar concentrations whereas the latter only causes lysis above, and often substantially above, its critical micellar concentration. In their respective ranges of lytic concentrations, both bile salts are far less effective with membranes of low fluidity. The results are discussed with regard to the features of a membrane which would be expected to be resistant to high concentrations of bile salts in vivo, i.e., the plasma membranes of the bile canaliculus and lumenal surface of biliary tract cells.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006000:Glycocholic Acid / Q000494:pharmacology; D006002:Glycodeoxycholic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000097:blood; D051381:Rats; D012756:Sheep; D013045:Species Specificity; D013552:Swine
D001647:Bile Acids and Salts; D008081:Liposomes; D008563:Membrane Lipids; D006002:Glycodeoxycholic Acid; D006000:Glycocholic Acid