title: Differential gene regulation of renal salt entry pathways by salt load in the distal nephron of the rat.
abstract: The aim of the present study was to determine the molecular responses of the main salt-reabsorbing systems in the distal nephron to changes of salt load of the organism. For this purpose we analysed messenger ribonucleic acid (mRNA) levels for the bumetanide-sensitive Na+K+2Cl- cotransporter (BSC1), the thiazide-sensitive Na+Cl- cotransporter (TSC), the kidney-specific inwards rectifier K+ channel (ROMK), the amiloride-sensitive epithelial Na+ channel (ENaC) and the kidney-specific Cl- channel ClC-K2, in the cortex and inner and outer medulla of kidneys from male Sprague-Dawley rats fed a high- (8% w/w), normal- (0.6%) or low-(0.02%) salt diet or treated chronically with subcutaneous infusions of furosemide (12 mg/kg per day). BSC1 and ROMK mRNA levels did not differ between the four treatment groups. TSC mRNA increased during furosemide treatment 1.75-fold versus control but was not affected by a high- or a low-salt diet. The mRNA for the alpha-subunit of ENaC increased with the low-salt diet (about 1.5-fold) and with furosemide (about 2.1-fold) in all kidney zones, but did not change with the high-salt diet. Dietary salt loading down-regulated CIC-K2 mRNA in the outer medulla 0.6-fold versus control whilst furosemide treatment, but not the low-salt diet, increased ClC-K2 mRNA in the outer (1.6-fold) and inner medulla (2.0-fold). These findings suggest that gene expression of Na+ and Cl- entry pathways in the distal nephron are at least partly regulated by the salt load of the organism, such that salt-reabsorbing systems are stimulated by salt deficiency and suppressed by salt overload.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, Germany. konrad.worlf@vkl.uni-regensburg.de
authors.forename: K
authors.initials: K
authors.lastname: Wolf
authors.forename: H
authors.initials: H
authors.lastname: Castrop
authors.forename: G A
authors.initials: GA
authors.lastname: Riegger
authors.forename: A
authors.initials: A
authors.lastname: Kurtz
authors.forename: B K
authors.initials: BK
authors.lastname: Krämer
mesh_terms: D000818:Animals; D000090007:CLC-2 Chloride Channels; D002352:Carrier Proteins / Q000235:genetics; D018118:Chloride Channels / Q000235:genetics; D053503:Epithelial Sodium Channels; D005786:Gene Expression Regulation / Q000502:physiology*; D007672:Kidney Cortex / Q000502:physiology; D007679:Kidney Medulla / Q000502:physiology; D008297:Male; D009399:Nephrons / Q000502:physiology*; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D049992:Sodium Chloride Symporters; D017673:Sodium Chloride, Dietary / Q000493:pharmacokinetics*; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D000090007:CLC-2 Chloride Channels; D002352:Carrier Proteins; D018118:Chloride Channels; D053503:Epithelial Sodium Channels; C510692:Kcnj1 protein, rat; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D011955:Receptors, Drug; C578716:Slc12a1 protein, rat; C578876:Slc12a3 protein, rat; D015222:Sodium Channels; D049992:Sodium Chloride Symporters; D017673:Sodium Chloride, Dietary; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor