Impaired ability to increase water excretion in mice lacking the taurine transporter gene TAUT

Abstract

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.

Microinjection of Glycine into the Hypothalamic Paraventricular Nucleus Produces Diuresis, Natriuresis, and Inhibition of Central Sympathetic Outflow

“…Marked increases in urine output and free-water clearance in response to glycine in the PVN suggest that this neurotransmitter may have an inhibitory influence on magnocellular neuronal activity and the release of AVP into the systemic circulation. This possibility is also suggested by the observation that taurine, which has affinity for glycine receptors, has an inhibitory influence on rat SON magnocellular neurons in vitro (Hussy et al, 2000) and in vivo (Huang et al, 2006). In accordance with this premise, we demonstrated that lowdose intravenous AVP infusion prevented the diuretic (and natriuretic) response to microinjection of glycine into the PVN.…”

PKD1 Haploinsufficiency Causes a Syndrome of Inappropriate Antidiuresis in Mice

“…To the best of our knowledge, there are no genetically modified mice with such an antidiuresis phenotype at baseline. An impaired ability to lower urine osmolality and increase urinary water excretion was recently reported in mice that lack the taurine transporter gene Taut (57), which could play a role in primary cilia (58). Thus, in addition to the interactions between polycystins and calcium signaling pathways, the Pkd1 ϩ/Ϫ mice could give insights into the mechanisms that govern osmoregulation, AVP signaling, and trafficking of AQP2 in the CD.…”

LC-MS/MS Analysis of Apical and Basolateral Plasma Membranes of Rat Renal Collecting Duct Cells

“…Based on the high quality of the spectra, we conclude here that the gastric isoform is expressed in the rat IMCD, although this identification does not exclude the presence of the colonic isoform as well. TauT, a sodium-and chloride-dependent taurine transporter, is an interesting protein because mice lacking TauT have impaired ability to increase water excretion in response to water loading (36). Another potential apical membrane marker protein is the GPI-linked membrane protein lipoprotein lipase (Table II).…”