Impaired ability to increase water excretion in mice lacking the taurine transporter gene TAUT.
Cellular taurine uptake or release counteracts alterations of cell volume. Na+-coupled taurine transporter TAUT mediates concentrative cellular uptake of taurine. Inhibition of vasopressin secretion by hypotonicity may involve taurine release from glial cells of supraoptic nucleus. We compared renal function of mice lacking TAUT (taut-/-) and wild-type littermates (taut+/+). We observed renal taurine loss and subsequent hypotaurinemia in taut-/- mice. With free access to water, plasma and urine osmolality, urinary flow rate as well as urinary excretion and plasma concentrations of Na+ and K+ were similar in taut-/- and taut+/+ mice, whereas plasma concentrations of urea were enhanced in taut-/- mice. An oral water load (1 ml/16 g body weight) induced a similar diuresis in both genotypes. Repeating the oral water load immediately after normalization of urine flow rate, however, resulted in delayed diuresis and higher urinary vasopressin/creatinine ratios in taut-/- mice. In comparison, the repeated diuretic response to vasopressin V2 receptor blockade was not different between genotypes. Water deprivation for 36 h led to similar antidiuresis and increases of urinary osmolality in both genotypes. Upon free access to water after deprivation, taut-/- mice continued to concentrate urine up to 6 days, while taut+/+ mice rapidly returned to normal urinary osmolality. Urinary vasopressin/creatinine ratios and plasma aldosterone concentrations were not different under basal conditions but were significantly higher in taut-/- mice than in taut+/+ mice at 6 days after water deprivation. In conclusion, taut-/- mice suffer from renal taurine loss and impaired ability to lower urine osmolality and to increase urinary water excretion. The latter defect could reside extrarenally and result from a role of taurine in the suppression of vasopressin release which may be attenuated in taut-/- mice.
Huang
Dan Yang
DY
Department of Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
Boini
Krishna M
KM
Lang
Philipp A
PA
Grahammer
Florian
F
Duszenko
Michael
M
Heller-Stilb
Birgit
B
Warskulat
Ulrich
U
Häussinger
Dieter
D
Lang
Florian
F
Vallon
Volker
V
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D005260:Female; D005440:Fluid Therapy; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D014867:Water / Q000378:metabolism*; D014868:Water Deprivation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology*; D000099247:Taurine Transporters
D065092:Antidiuretic Hormone Receptor Antagonists; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D014867:Water; D000099247:Taurine Transporters