Effects of membrane fluidizing agents on renal brush border proton permeability.
H+ permeability (PH) of brush border membrane vesicles isolated from rabbit renal cortex was measured from the rate of collapse of preformed pH gradients using acridine orange fluorescence quenching. n-Alkanols increased PH from 0.005 to 0.1 cm/s in a dose-dependent manner. At 25 degrees C, PH increased to 0.01 cm/s at [n-alkanol] = 90 mM (butanol), 30 mM (pentanol), 7 mM (hexanol), and 1.8 mM (heptanol). Activation energy (Ea) of PH was 21.6 kcal/mol (5-50 degrees C), which decreased to 18.5 kcal/mol in the presence of either 200 mM butanol or 12 mM hexanol. Membrane fluidity was estimated from diphenylhexatriene anisotropy (r). n-Alkanols decreased r from 0.25 to 0.18 in a dose-dependent manner. At 25 degrees C, r = 0.22 at [n-alkanol] = 200 mM (butanol), 27 mM (pentanol), 9.5 mM (hexanol), and 2 mM (heptanol). The effects of n-alkanols on PH and r correlated well with known n-alkanol lipid-water partition coefficients. Similar increases in PH and decreases in r were observed for nonalkanol lipid anesthetics. The effects of n-alkanols on the Na+-H+ antiporter and on osmotically driven water transport were also studied. At concentrations of n-alkanol that resulted in a 10-fold increase in PH, there was no significant effect on either Na+-H+ exchange or water transport. These results suggest a lipid pathway for brush border H+ diffusion that is distinct from both the Na+-H+ antiporter and the water transport pathway.
D020001:1-Butanol; D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active; D000440:Butanols / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002725:Chloroform / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D019850:Heptanol; D000441:Hexanols / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism*; D007672:Kidney Cortex / Q000648:ultrastructure*; D008433:Mathematics; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D000439:Pentanols / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
D000438:Alcohols; D000440:Butanols; D000441:Hexanols; D008563:Membrane Lipids; D000439:Pentanols; D000431:Ethanol; C036260:1-hexanol; D002725:Chloroform; D006859:Hydrogen; D019850:Heptanol; D020001:1-Butanol; D012964:Sodium; C024999:n-pentanol