title: Regulation of the Cl-/HCO3- exchanger AE2 in rat thick ascending limb of Henle's loop in response to changes in acid-base and sodium balance.
abstract: The Cl(-)/HCO(3)(-) exchanger AE2 is believed to be involved in transcellular bicarbonate reabsorption that occurs in the thick ascending limb of Henle's loop (TAL). The purpose of this study was to test whether chronic changes in acid-base status and sodium intake regulate AE2 polypeptide abundance in the TAL of the rat. Rats were subjected to 6 d of loading with NaCl, NH(4)Cl, NaHCO(3), KCl, or KHCO(3). AE2 protein abundance was estimated by semiquantitative immunoblotting in renal membrane fractions isolated from the cortex and the outer medulla of treated and control rats. In the renal cortex, AE2 abundance was markedly increased in response to oral loading with NH(4)Cl or with NaCl. In contrast, AE2 abundance was unchanged in response to loading with KCl or with NaHCO(3) and was decreased by loading with KHCO(3). The response of AE2 in the outer medulla differed from that in the cortex in that HCO(3)(-) loading increased AE2 abundance when administered with Na(+) but had no effect when administered with K(+). Immunohistochemistry revealed that NaCl loading increased AE2 abundance in the basolateral membrane of both the cortical and the medullary TAL. In contrast, NH(4)Cl loading increased AE2 abundance only in the cortical TAL but not in the medullary TAL. These results suggest that regulation of the basolateral Cl(-)/HCO(3)(-) exchanger AE2 plays an important role in the adaptation of bicarbonate absorption in the TAL during chronic acid-base disturbances and high sodium intake. The present study also emphasizes the contribution of cortical TAL adaptation in the renal regulation of acid-base status.
authors.affiliation: Unité INSERM 356, Institut de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75270 Paris Cedex 06, France. chambrey@ccr.jussieu.fr
authors.forename: Fabienne
authors.initials: F
authors.lastname: Quentin
authors.forename: Dominique
authors.initials: D
authors.lastname: Eladari
authors.forename: Sebastian
authors.initials: S
authors.lastname: Frische
authors.forename: Michèle
authors.initials: M
authors.lastname: Cambillau
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
authors.forename: Michel
authors.initials: M
authors.lastname: Paillard
authors.forename: Régine
authors.initials: R
authors.lastname: Chambrey
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology*; D000138:Acidosis / Q000378:metabolism*; D000284:Administration, Oral; D000471:Alkalosis / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism*; D017920:Antiporters / Q000378:metabolism*; D001639:Bicarbonates / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D017680:Potassium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064606:SLC4A Proteins; D012964:Sodium / Q000378:metabolism*; D017693:Sodium Bicarbonate / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D001639:Bicarbonates; D017680:Potassium Compounds; D064606:SLC4A Proteins; D000643:Ammonium Chloride; D012965:Sodium Chloride; D011189:Potassium Chloride; D017693:Sodium Bicarbonate; D012964:Sodium; C026329:potassium bicarbonate