title: Impact of bicarbonate, ammonium chloride, and acetazolamide on hepatic and renal SLC26A4 expression.
abstract: SLC26A4 encodes pendrin, a transporter exchanging anions such as chloride, bicarbonate, and iodide. Loss of function mutations of SLC26A4 cause Pendred syndrome characterized by hearing loss and enlarged vestibular aqueducts as well as variable hypothyroidism and goiter. In the kidney, pendrin is expressed in the distal nephron and accomplishes HCO(3)(-) secretion and Cl(-) reabsorption. Renal pendrin expression is regulated by acid-base balance. The liver contributes to acid-base regulation by producing or consuming glutamine, which is utilized by the kidney for generation and excretion of NH(4)(+), paralleled by HCO(3)(-) formation. Little is known about the regulation of pendrin in liver. The present study thus examined the expression of Slc26a4 in liver and kidney of mice drinking tap water without or with NaHCO(3) (150 mM), NH(4)Cl (280 mM) or acetazolamide (3.6 mM) for seven days. As compared to Gapdh transcript levels, Slc26a4 transcript levels were moderately lower in liver than in renal tissue. Slc26a4 transcript levels were not significantly affected by NaHCO(3) in liver, but significantly increased by NaHCO(3) in kidney. Pendrin protein expression was significantly enhanced in kidney and reduced in liver by NaHCO(3). Slc26a4 transcript levels were significantly increased by NH(4)Cl and acetazolamide in liver, and significantly decreased by NH(4)Cl and by acetazolamide in kidney. NH(4)Cl and acetazolamide reduced pendrin protein expression significantly in kidney, but did not significantly modify pendrin protein expression in liver. The observations point to expression of pendrin in the liver and to opposite effects of acidosis on pendrin transcription in liver and kidney.
authors: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors: Ioana
authors: I
authors: Alesutan
authors: Arezoo
authors: A
authors: Daryadel
authors: Nilufar
authors: N
authors: Mohebbi
authors: Lisann
authors: L
authors: Pelzl
authors: Christina
authors: C
authors: Leibrock
authors: Jakob
authors: J
authors: Voelkl
authors: Soline
authors: S
authors: Bourgeois
authors: Silvia
authors: S
authors: Dossena
authors: Charity
authors: C
authors: Nofziger
authors: Markus
authors: M
authors: Paulmichl
authors: Carsten A
authors: CA
authors: Wagner
authors: Florian
authors: F
authors: Lang
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D001639:Bicarbonates / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D001639:Bicarbonates; D012333:RNA, Messenger; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters; D000643:Ammonium Chloride; D000086:Acetazolamide