Taurine Influx Research Articles

Significance of taurine transporter (TauT) in homeostasis and its layers of regulation (Review).

Taurine (2-aminoethanesulfonic acid) contributes to homeostasis, mainly through its antioxidant and osmoregulatory properties. Taurine's influx and efflux are mainly mediated through the ubiquitous expression of the sodium/chloride-dependent taurine transporter, located on the plasma membrane. The significance of the taurine transporter has been shown in various organ malfunctions in taurine-transporter-null mice. The taurine transporter differentially responds to various cellular stimuli including ionic environment, electrochemical charge, and pH changes. The renal system has been used as a model to evaluate the factors that significantly determine the regulation of taurine transporter regulation.

Imidazole-4-acetic acid, a new lead structure for interaction with the taurine transporter in outer blood-retinal barrier cells

Retinal diseases leading to impaired vision and ultimately blindness are mainly characterized by ischemic and hypoxic stress. Targeting the retinal ρ-containing γ-aminobutyric acid type A receptors (ρ GABAARs) and thereby decreasing the retinal neuronal activity has been proposed as a novel therapeutic approach. The taurine transporter (TAUT) plays a key role in the retinal transport of GABA and has been previously suggested to display a higher functional activity in the retina compared to the brain. TAUT would therefore stand as a suitable target for the selective delivery of ρ GABAAR ligands into the retina. Consequently, an in vitro model of TAUT at the outer blood-retinal barrier (BRB) was developed and characterized using the ARPE-19 cell line. Furthermore, the structural requirements of GABAAR ligands for interacting with TAUT at the BRB were investigated for a series of standard GABAAR ligands by testing their ability to inhibit the TAUT-mediated influx of taurine in ARPE-19 cells. Results showed that taurine influx was seven-fold higher when the ARPE-19 cells were cultured under hyperosmotic conditions and was demonstrated to display saturable kinetics (Km=27.7±2.2μM and Jmax=24.2±0.6pmol/cm2·min). Furthermore, the taurine influx was significantly inhibited in a concentration-dependent manner by GABA and imidazole-4-acetic acid (IAA), which is a naturally occurring metabolite of histamine. These compounds display similar Ki values of 644.2μM and 658.6μM, respectively. Moreover, IAA demonstrated higher inhibitory properties than the other tested GABA analogs: 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), 4,5,6,7-tetrahydropyrazolo[5,4-c]pyridin-3-ol (Aza-THIP), muscimol, and thiomuscimol. These studies demonstrated that IAA interacts with TAUT, which makes IAA a new lead structure in the development of new compounds, which are not only interacting with TAUT but also potent ρ GABAAR ligands.

Downregulation of the Taurine Transporter TauT During Hypo-Osmotic Stress in NIH3T3 Mouse Fibroblasts

The present work was initiated to investigate regulation of the taurine transporter TauT by reactive oxygen species (ROS) and the tonicity-responsive enhancer binding protein (TonEBP) in NIH3T3 mouse fibroblasts during acute and long-term (4 h) exposure to low-sodium/hypo-osmotic stress. Taurine influx is reduced following reduction in osmolarity, keeping the extracellular Na+ concentration constant. TonEBP activity is unaltered, whereas TauT transcription as well as TauT activity are significantly reduced under hypo-osmotic conditions. In contrast, TonEBP activity and TauT transcription are significantly increased following hyperosmotic exposure. Swelling-induced ROS production in NIH3T3 fibroblasts is generated by NOX4 and by increasing total ROS, by either exogenous application of H2O2 or overexpressing NOX4, we demonstrate that TonEBP activity and taurine influx are regulated negatively by ROS under hypo-osmotic, low-sodium conditions, whereas the TauT mRNA level is unaffected. Acute exposure to ROS reduces taurine uptake as a result of modulated TauT transport kinetics. Thus, swelling-induced ROS production could account for the reduced taurine uptake under low-sodium/hypo-osmotic conditions by direct modulation of TauT.Electronic supplementary materialThe online version of this article (doi:10.1007/s00232-012-9416-8) contains supplementary material, which is available to authorized users.

Taurine Biosynthesis by Neurons and Astrocytes

The physiological roles of taurine, a product of cysteine degradation and one of the most abundant amino acids in the body, remain elusive. Taurine deficiency leads to heart dysfunction, brain development abnormalities, retinal degradation, and other pathologies. The taurine synthetic pathway is proposed to be incomplete in astrocytes and neurons, and metabolic cooperation between these cell types is reportedly needed to complete the pathway. In this study, we analyzed taurine synthesis capability as reported by incorporation of radioactivity from [(35)S]cysteine into taurine, in primary murine astrocytes and neurons, and in several transformed cell lines (human (SH-SY5Y) and murine (N1E-115) neuroblastoma, human astrocytoma (U-87 MG and 1321 N1), and rat glioma (C6)). Extensive incorporation of radioactivity from [(35)S]cysteine into taurine was observed in rat glioma cells as well as in primary mouse astrocytes and neurons, establishing the presence of an intact taurine synthesis pathway in these cells. Interestingly, exposure of cells to cysteine or cysteamine resulted in elevated intracellular hypotaurine without a corresponding increase in taurine levels, suggesting that oxidation of hypotaurine limits taurine synthesis in cells. Consistent with its role as an organic osmolyte, taurine synthesis was stimulated under hypertonic conditions in neurons.

Muscarinic receptor regulation of osmosensitive taurine transport in human SH‐SY5Y neuroblastoma cells

The ability of G‐protein‐coupled receptors to regulate osmosensitive uptake of the organic osmolyte, taurine, into human SH‐SY5Y neuroblastoma cells has been examined. When monitored under isotonic conditions taurine influx was mediated exclusively by a Na+‐dependent, high‐affinity (Km=2.5 μM) saturable transport mechanism (Vmax=0.087 nmol/mg protein/min). Reductions in osmolarity of >20% (under conditions of constant NaCl) resulted in an inhibition of taurine influx (>30%) that could be attributed to a reduction in Vmax, whereas the Km for uptake remained unchanged. Inclusion of the muscarinic cholinergic agonist, oxotremorine‐M (Oxo‐M), also resulted in an attenuation of taurine influx (EC50~0.7 μM). Although Oxo‐M‐mediated inhibition of taurine uptake could be observed under isotonic conditions (~25‐30%), the magnitude of inhibition was significantly enhanced by hypotonicity (~55‐60%), a result that also reflected a reduction in the Vmax, but not the Km, for taurine transport. Oxo‐M‐mediated inhibition of taurine uptake was dependent upon the availability of extracellular Ca2+ but was independent of protein kinase C activity. These results suggest that taurine uptake is reduced upon muscarinic receptor activation in a volume‐dependent fashion, thus facilitating taurine depletion from cells upon exposure to hypotonicity. Supported by NS23831 (SKF) GM007767 (DJF) and DK64959 (RB).

Muscarinic receptor regulation of osmosensitive taurine transport in human SH‐SY5Y neuroblastoma cells

The ability of G protein-coupled receptors to regulate osmosensitive uptake of the organic osmolyte, taurine, into human SH-SY5Y neuroblastoma cells has been examined. When monitored under isotonic conditions and in the presence of physiologically relevant taurine concentrations (1-100 microM), taurine influx was mediated exclusively by a Na(+)-dependent, high-affinity (K(m) = 2.5 microM) saturable transport mechanism (V(max) = 0.087 nmol/mg protein/min). Reductions in osmolarity of > 20% (attained under conditions of a constant NaCl concentration) resulted in an inhibition of taurine influx (> 30%) that could be attributed to a reduction in V(max), whereas the K(m) for uptake remained unchanged. Inclusion of the muscarinic cholinergic agonist, oxotremorine-M (Oxo-M), also resulted in an attenuation of taurine influx (EC(50) approximately 0.7 microM). Although Oxo-M-mediated inhibition of taurine uptake could be observed under isotonic conditions (approximately 25-30%), the magnitude of inhibition was significantly enhanced by hypotonicity (approximately 55-60%), a result that also reflected a reduction in the V(max), but not the K(m), for taurine transport. Oxo-M-mediated inhibition of taurine uptake was dependent upon the availability of extracellular Ca(2+) but was independent of protein kinase C activity. In addition to Oxo-M, inclusion of either thrombin or sphingosine 1-phosphate also attenuated volume-dependent taurine uptake. The ability of Oxo-M to inhibit the influx of taurine was attenuated by 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid, an inhibitor of the volume-sensitive organic osmolyte and anion channel. 4-[(2-Butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid also prevented receptor-mediated changes in the efflux and influx of K(+) under hypoosmotic conditions. The results suggest that muscarinic receptor activation can regulate both the volume-dependent efflux and uptake of taurine and that these events may be functionally coupled.

Casein kinase 2 regulates the active uptake of the organic osmolyte taurine in NIH3T3 mouse fibroblasts

Inhibition of the constitutively active casein kinase 2 (CK2) with 2-dimethyl-amino-4,5,6,7-tetrabromo-1H-benzimidasole stimulates the Na(+)-dependent taurine influx via the taurine transporter TauT in NIH3T3 cells. CK2 inhibition reduces the TauT mRNA level and increases the localization of TauT to ER but has no detectable effect on TauT protein expression. On the other hand, CK2 inhibition increases the affinity of TauT towards Na(+ )and reduces the Na(+)/taurine stoichiometry for active taurine uptake. It is suggested that CK2 controls the cellular taurine uptake in unperturbated NIH3T3 cells, i.e., inhibition of CK2 increases the affinity of TauT towards Na(+) and hence Na(+)-dependent taurine uptake.

High Affinity Transport of Taurine by the Drosophila Aspartate Transporter dEAAT2

Excitatory amino acid transporters (EAATs) are structurally related plasma membrane proteins known to mediate the Na(+)/K(+)-dependent uptake of the amino acids l-glutamate and dl-aspartate. In the nervous system, these proteins contribute to the clearance of glutamate from the synaptic cleft and maintain excitatory amino acid concentrations below excitotoxic levels. Two homologues exist in Drosophila melanogaster, dEAAT1 and dEAAT2, which are specifically expressed in the nervous tissue. We previously reported that dEAAT2 shows unique substrate discrimination as it mediates high affinity transport of aspartate but not glutamate. We now show that dEAAT2 can also transport the amino acid taurine with high affinity, a property that is not shared by two other transporters of the same family, Drosophila dEAAT1 and human hEAAT2. Taurine transport by dEAAT2 was efficiently blocked by an EAAT antagonist but not by inhibitors of the structurally unrelated mammalian taurine transporters. Taurine and aspartate are transported with similar K(m) and relative efficacy and behave as mutually competitive inhibitors. dEAAT2 can mediate either net uptake or the heteroexchange of its two substrates, both being dependent on the presence of Na(+) ions in the external medium. Interestingly, heteroexchange only occurs in one preferred substrate orientation, i.e. with taurine transported inwards and aspartate outwards, suggesting a mechanism of transinhibition of aspartate uptake by intracellular taurine. Therefore, dEAAT2 is actually an aspartate/taurine transporter. Further studies of this protein are expected to shed light on the role of taurine as a candidate neuromodulator and cell survival factor in the Drosophila nervous system.

Separate taurine and chloride efflux pathways activated during regulatory volume decrease.

Organic osmolyte and halide permeability pathways activated in epithelial HeLa cells by cell swelling were studied by radiotracer efflux techniques and single-cell volume measurements. The replacement of extracellular Cl- by anions that are more permeant through the volume-activated Cl- channel, as indicated by electrophysiological measurements, significantly decreased taurine efflux. In the presence of less-permeant anions, an increase in taurine efflux was observed. Simultaneous measurement of the 125I, used as a tracer for Cl-, and [3H]taurine efflux showed that the time courses for the two effluxes differed. In Cl--rich medium the increase in I- efflux was transient, whereas that for taurine was sustained. Osmosensitive Cl- conductance, assessed by measuring changes in cell volume, increased rapidly after hypotonic shock. The influx of taurine was able to counteract Cl- conductance-dependent cell shrinkage but only approximately 4 min after triggering cell swelling. This taurine-induced effect was blocked by DIDS. Differences in anion sensitivity, the time course of activation, and sensitivity to DIDS suggest that the main cell swelling-activated permeability pathways for taurine and Cl- are separate.

Calyculin A modulates the kinetic constants for the Na +-coupled taurine transport in Ehrlich ascites tumour cells

The effect of the phosphatase inhibitor calyculin A (cal A) on the kinetic parameters of the Na +-coupled taurine uptake via the taurine transporter in the Ehrlich ascites tumour cells has been investigated. Preincubation with cal A (100 nM) reduces the initial taurine influx by about 20%, but has no effect on the diffusional component of the taurine influx or on the taurine release from cells suspended in isotonic or in hypotonic medium. Thus, cal A-sensitive phosphatases only affect taurine transport mediated by the Na +-dependent taurine transporter. Cal A increases the Michaelis–Menten constant for binding of taurine to the transporter from 31±6 to 45±4 μM and reduces the taurine transport capacity from 210±20 to 170±10 pmol×g dry wt −1×min −1. The Michaelis–Menten constant for binding of Na + to the taurine transporter is concomitantly increased from 96±11 to 129±8 mM and the Na +:taurine coupling ratio for activation of the transport cycle is reduced from 3.3±0.6 to 2.4±0.2. This suggests that cal A-sensitive phosphatases maintain a high affinity of the taurine transporter towards Na + and taurine as well as a high taurine transport capacity in unpertubated Ehrlich cells.

Volume-activated taurine transport is differentially activated in human cervical cancer HT-3 cells but not in human papillomavirus-immortalized Z183A and normal cervical epithelial cells.

1. Previous studies demonstrate that volume-sensitive chloride currents are distinctly activated in cervical cancer cells, but not in human papillomavirus (HPV)-immortalized and normal cervical cells. In the present study, the Na(+)-independent volume-activated transport of taurine in three cervical cell types was investigated. 2. Osmotic swelling of cervical cancer HT-3 cells suspended in Na(+)-free hypotonic medium led to increased membrane uptake of taurine. This taurine uptake was effectively blocked by various Cl- channel blockers with a similar potency in blocking volume-sensitive Cl- channels: 1,9-dideoxyforskolin > 5-nitro-2-(3-phenyl-propylamino)-benzoic acid (NPPB) > 4-acetamido-4'-isothiocyanastilbene-2,2'-disulphonic acid (SITS) > 4,4'-diisothio-cyanatostilbene-2,2-disulphonic acid (DIDS) > furosemide. The taurine influx was also abolished by pertussis toxin. In contrast, Na(+)-independent volume-activated taurine transport was not significantly activated in HPV-immortalized Z183A cells and in normal cervical cells. 3. Exposure of HT-3 cells to hypotonic medium also resulted in a marked increase in taurine efflux. The volume-activated taurine efflux was osmolarity dependent and the pattern of pharmacological inhibition by Cl- channel blockers was indistinguishable from that for taurine uptake. 4. These results suggest that volume-sensitive Cl- channels in HT-3 cells can mediate the transport of amino acids. In addition, the pertussis toxin-sensitive G-protein is linked with the activation of this transport mechanism.

Regulation of taurine accumulation in the ciliate protozoanTetrahymena pyriformis

Tetrahymena pyriformis suspended in an inorganic medium accumulates3H-labelled taurine against a concentration gradient resulting in a cellular to extracellular taurine gradient of about 3 within 2 hours. This is observed in spite of the fact that taurine influx inTetrahymena via the saturable, Na1-dependent system and the leak pathway becomes gradually reduced with time after transfer to an inorganic, taurine free medium. Taurine is not accumulated byTetrahymena at pH below 7.0 or when protein synthesis is prevented by addition of cycloheximide. Addition of actinomycin D has no effect on the taurine accumulation. It is suggested that the transporter responsible for taurine accumulation inTetrahymena has a pH threshold of 7.0 and that translation but not transcription is conditional for the emergence of the transporter following transfer to inorganic medium. Taurine accumulation is reduced when the phosphatase inhibitor calyculin A is added at the initiation of starvation but unaffected when the inhibitor is added once the cells are in the inorganic medium. Addition of forskolin significantly enhances taurine accumulation. It is proposed that phosphorylation as well as dephosphorylation are involved in the regulation of taurine accumulation inTetrahymena pyriformis.

Taurine transport systems in the ciliate protozoanTetrahymena pyriformis

Tetrahymena pyriformis cultivated in the presence of 1 mM taurine prior to transfer of the cells to non-nutrient medium express an enhanced capacity for concentrative taurine uptake and for taurine diffusion compared to cells grown without added taurine. The unidirectional taurine influx in taurine-grown cells comprises a saturable component with Km -257μM, Vmax = 21 n-moles · g dry wt−1 sd min−1, and a diffusion component with a diffusion constant of 0.20 ml · g dry wt−1 · min−1. At extracellular taurine concentrations <30μM, 20% of the influx is via the saturable system and 80% is via the diffusion system. 19% of the influx in Na+-dependent, Cl−-independent, and not inhibitable with structural analogues to taurine, suggesting that the transport system responsible for the saturable component in Tetrahymena is different from the Na+- and Cl−-dependent taurine translocating system (theβ-system) described in vertebrate cells. The unidirectional taurine influx is reduced by 80% by 1mM DIDS (inhibitor of anion exchange and anion channels) and by 1 mM MK196 (indachrinone, inhibitor of anion channels) indicating that taurine diffusion inTetrahymena is via a channel, which is permanently active and which resembles the swelling-induced “taurine channel” seen in mammalian cells. Taurine influx is stimulated by the forskolin analogue 1,9-dideoxyforskolin and by arachidonic acid, and this stimulation is in both cases sensitive to DIDS and MK196.

Volume-activated taurine permeability in cells of the human erythroleukemic cell line K562.

The effects of hypotonic shock on cell volume, taurine influx and efflux were examined in the human erythroleukemic cell line K562. Cells exposed to hypotonic solutions exhibited a regulatory volume decrease (RVD) following rapid increases in cell volume. Cell swelling was associated with a increased taurine influx and efflux. The volume-activated taurine pathway was Na(+)-independent, and increased in parallel with increasing cell volume. The chloride channel blocker, 2,5-dichlorodiphenylamine-2-carboxylic acid (DCDPC), completely blocked the volume-activated taurine influx and efflux, while [dihydroindenyl)oxy]alkanoic acids (DIOA) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), an anion exchanger and anion channel blocker, respectively, also inhibited significantly. These results suggest that taurine transport is increased in response to hypotonic stress, which may be mediated via a volume-activated, DCDPC-sensitive anion channel.

Phosphorylation is involved in the regulation of the taurine influx via the beta-system in Ehrlich ascites tumor cells.

The role of 3',5'-cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), protein kinase C (PKC) and phosphatases in the regulation of the taurine influx via the beta-system in Ehrlich ascites tumor cells has been investigated. The taurine uptake by the beta-system in Ehrlich cells is inhibited when PKC is activated by phorbol 12-myristate 13-acetate (PMA) and when protein phosphatases are inhibited by calyculin A (CLA). On the other hand, taurine uptake by the beta-system is stimulated by an increased level of cAMP or following addition of N6,2'-O-dibutyryl-3',5'-cyclic adenosine monophosphate (dbcAMP). The effect of dbcAMP is partially blocked by addition of the protein kinase inhibitor H-89, and suppressed in the presence of CLA. It is proposed that the beta-system in the Ehrlich cells exists in three states of activity: State I, where a PKC phosphorylation site on the transporter or on a regulator is phosphorylated and transport activity is low. State II, where the PKC phosphorylation site is dephosphorylated and transport activity is normal. State III, representing a state with high transport activity, induced by an elevated cellular cAMP level. Apparently, cAMP preferentially stimulates taurine transport when the beta-system is in State II.

Taurine efflux is a cell volume regulatory process in proximal renal tubules from the teleost Carassius auratus.

The potential role of taurine transport associated with volume regulation in renal tissue and isolated proximal renal tubules was studied in the teleost Carassius auratus (goldfish). The cellular taurine content in renal tissue fragments incubated in isosmotic solution (290 mOsm) (7.8 +/- 0.9 (SD) micromol g wet wt(-1)) decreased by 60% following exposure to hyposmotic medium (100 mOsm). The rate coefficient for [14C]taurine efflux in renal tissue and in isolated proximal renal tubules was strongly stimulated following hyposmotically or urea-activated cellular swelling. The stimulated basolateral taurine efflux pathway exhibited channel-like functional characteristics since (a) [14C]taurine influx was stimulated in parallel with the osmolality-dependent taurine efflux and (b) this efflux could not be stimulated by high medium taurine concentrations (40 mM) applied 10 min following the osmolality reduction (trans-stimulation test). Administration of the 5-lipoxygenase inhibitor ETH 615-139 (20 microM) during hyposmotic stimulation inhibited regulatory volume decreases but had no effect on taurine efflux. In addition, hyposmotically induced taurine efflux was slightly but significantly inhibited by the cyclooxygenase inhibitor indomethacin (10 microM). The taurine efflux was also dependent on both extra- and intracellular Ca2+. It is concluded that taurine is likely to coparticipate with KCl as an osmoeffector during RVD in Carassius proximal renal tubule cells. Cellular swelling seems to activate a basolateral taurine transport pathway with functional properties of a channel. This efflux mechanism appears to be partly regulated by Ca2+. Such a transport pathway could play a role in the cell volume regulatory mechanisms participating during transepithelial solute and water transport.

Taurine transport at the blood-brain barrier: an in vivo brain perfusion study

Taurine transport into six brain regions of equithesin-anesthetized rats was studied by the in situ brain perfusion technique. This technique gives both accurate measurements of cerebrovascular amino acid transport and allows complete control of the perfusate amino acid composition. Final wash procedure showed that taurine efflux occurred rapidly from endothelial cells. The taurine influx into endothelial cells was sodium and chloride dependent suggesting that the sodium and chloride gradients are the principal source of energy for taurine transport into endothelial cells. Taurine transport could be fitted by a model with saturable components. The kinetic constants in the parietal cortex were 1.4 × 10 −4 μmol/s/g for the apparent V max and 0.078 mM for the apparent K m . Competition experiments in the presence of sodium ions showed that [ 14C]taurine uptake was strongly inhibited by the structural analogs of taurine, hypotaurine and β-alanine.

Blood-brain barrier taurine transport during osmotic stress and in focal cerebral ischemia.

Little is known about blood to brain taurine transport despite substantial evidence suggesting a role of taurine in brain volume regulation during osmotic stress or conditions inducing cell swelling, such as ischemia. We have made measurements of the taurine influx rate constant (K1) with [3H]taurine in three conditions: raised plasma taurine concentrations induced by infusion with 50 mM taurine (10 microliters/100 g/min); osmotic stress induced by i.p. injections of 1.5 M NaCl (2 ml/100 g) or distilled water (10 ml/100 g); and 4 h of middle cerebral artery occlusion (MCAo). In rats with MCAo, additional determinations were made of tissue water and taurine contents, and blood-brain barrier passive permeability with [3H]alpha-aminoisobutyric acid. Taurine infusion increased plasma taurine from 110 +/- 63 microM (SD) to 407 +/- 63 (p < 0.001) and decreased taurine K1 at the blood-brain barrier by 70% (p < 0.001), signifying saturable uptake that maintained unidirectional influx constant. Similarly, although hypo- and hyperosmolality increased and decreased plasma taurine concentration, respectively, a reciprocal relationship between K1 and plasma taurine in these experiments ensured that unidirectional fluxes of taurine into brain were unchanged by osmotic stress. During MCAo, the taurine K1 was reduced 80% in the ipsilateral ischemic tissue compared with the contralateral nonischemic tissue (p < 0.001). This decline may be due to a release of taurine into the brain circulation, because there was a concomitant loss of tissue taurine of 7.4 +/- 2.4 mmol/g dry weight (p < 0.05). Alternately, if taurine uptake is sodium dependent, the decline might reflect a disruption of the endothelial sodium gradient.

Identification of a high affinity taurine transporter which is not dependent on chloride.

Taurine transport by lactating gerbil mammary tissue has been examined. Taurine uptake is mediated by a high-affinity system which is specific for beta-amino acids. The uptake of taurine is Na(+)-dependent but appears not to be obligatory dependent upon Cl-. Thus, replacing Na+ with choline almost abolished taurine uptake. Substituting Cl- with NO3- had no effect whereas SCN- induced a small but significant increase in taurine influx. Taurine uptake was Na(+)-dependent under conditions where Cl- had been replaced with NO3-. However, it is apparent that the Na(+)-dependent taurine transport system requires the presence of a permeable anion because replacing Cl- with gluconate markedly reduced taurine uptake. Cell-swelling, induced by a hyposmotic challenge, increased the efflux of taurine from gerbil mammary tissue via a pathway sensitive to niflumic acid.

Beta-amino acid transport in pig small intestine in vitro by a high-affinity, chloride-dependent carrier

This study describes unidirectional influx of amino acids and d-glucose across the small intestinal brush-border membrane of fully weaned eight week old pigs. Influx is minimal in the duodenum and maximal in the distal and/or mid small intestine. Influx of β-alanine, taurine and N-ethyl-aminoisobutyric acid is chloride-dependent. The activation stoichiometry for taurine influx is 1.0 ± 0.2 chloride/2.4 ± 0.3 sodium/ 1 taurine. Influx of D-glucose, lysine, glycine and glutamate is chloride-independent. An ABC test demonstrates a common β-amino acid carrier: (a) the apparent affinity constant K 1 2 Taurine is 44 ± 13 μM (means ± S.D.) and the inhibitory constant ( K i Taurine) against β-alanine influx is 41 ± 5 μM (means ± S.E.). (b) K 1 2 β- alanine is 97 ± 23 μM and K i β-alanine against taurine influx is 160 ± 22 μM. (c) K i Hypotaunne against taurine and β-alanine influx is 43 ± 4 ( n = 7) and 22 ± 5 μM ( n = 7), respectively. In conclusion, a high affinity, low capacity, sodium- and chloride-dependent carrier of β-amino acids is present in pig small intestine.