title: Bicarbonate transport along the loop of Henle. I. Microperfusion studies of load and inhibitor sensitivity.
abstract: We microperfused the loop of Henle (LOH) to assess its contribution to urine acidification in vivo. Under control conditions (Na HCO3- = 13 mM, perfusion rate approximately 17 nl/min-1) net bicarbonate transport (JHCO3-) was unsaturated, flow- and concentration-dependent, and increased linearly until a bicarbonate load of 1,400 pmol.min-1 was reached. Methazolamide (2 x 10(-4) M) reduced JHCO3 by 70%; the amiloride analogue ethylisopropylamiloride (EIPA) (2 x 10(-4) M) reduced JHCO3 by 40%; neither methazolamide nor EIPA affected net water flux (Jv). The H(+)-ATPase inhibitor bafilomycin A1 (10(-5) M) reduced JHCO3 by 20%; the Cl- channel inhibitor 5-nitro-2'-(3-phenylpropylamino)-benzoate (2 x 10(-4) M) and the Cl(-)-base exchange inhibitor diisothiocyanato-2,2'-stilbenedisulfonate (5 x 10(-5) M), had no effect on fractional bicarbonate reabsorption. Bumetanide (10(-6) M) stimulated bicarbonate transport (net and fractional JHCO3-) by 20%, whereas furosemide (10(-4) M) had no effect on bicarbonate reabsorption; both diuretics reduced Jv. In summary: (a) the LOH contributes significantly to urine acidification. It normally reabsorbs an amount equivalent to 15% of filtered bicarbonate; (b) bicarbonate reabsorption is not saturated; (c) Na(+)-H+ exchange and an ATP-dependent proton pump are largely responsible for the bulk of LOH bicarbonate transport.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510-8026.
authors.forename: G
authors.initials: G
authors.lastname: Capasso
authors.forename: R
authors.initials: R
authors.lastname: Unwin
authors.forename: S
authors.initials: S
authors.lastname: Agulian
authors.forename: G
authors.initials: G
authors.lastname: Giebisch
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000042:Absorption; D000136:Acid-Base Equilibrium; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D008138:Loop of Henle / Q000378:metabolism*; D018942:Macrolides; D008297:Male; D008704:Methazolamide / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D010477:Perfusion; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000900:Anti-Bacterial Agents; D001639:Bicarbonates; D018942:Macrolides; D009579:Nitrobenzoates; D002034:Bumetanide; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C039465:5-dimethylamiloride; D000584:Amiloride; D005665:Furosemide; C040929:bafilomycin A1; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D008704:Methazolamide