Bicarbonate transport along the loop of Henle. I. Microperfusion studies of load and inhibitor sensitivity.
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.
Capasso
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Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510-8026.
Unwin
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R
Agulian
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Giebisch
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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
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