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At least 19 recordsLinked to original sources
PubMed1988

Use of progress curves to estimate the co-substrate-to-substrate flow ratio of a symport mechanism. Application to the isoleucine-Na+ symport of mouse ascites-tumour cells and to the lactose-proton symport.

The model envisages two components in the process, whereby Ht equivalents of co-substrate and St equivalents of substrate accumulate in the cellular compartment in time t. The first is the flow through the symport, n equivalents of co-substrate entering or leaving with each substrate equivalent. The second is the basal flow of co-substrate outside the symport. In certain specific circumstances n can be derived by plotting Ht/t against St/t. The principal requirement is that, whereas the ratio of the component flows must change in the interval t, the magnitude of the basal flow must either be zero or constant. The procedure is applied to published observations [West & Mitchell (1973) Biochem. J. 132, 587-592] on the lactose-proton symport of Escherichia coli [n = 1.075 +/- 0.064(7)] and to new observations on the isoleucine-Na+ symport of mouse ascites-tumour cells [n = 1.136 +/- 0.120(18)].

Animals↗
PubMed1993

Thyroid hormone stimulates the Na(+)-PO4 symporter but not the Na(+)-SO4 symporter in renal brush border.

In our previous studies we established that thyroid hormones [L-thyroxine (T4) or 3,5,3'-triiodothyronine (T3)] elicit an increase in Na(+)-Pi symport in rat and mouse renal brush-border membrane (BBM) vesicles (BBMV), but the Na(+)-coupled symports of other solutes were not influenced. However, a recent report [H. S. Tenenhouse, J. Lee, and N. Harvey. Am. J. Physiol. 261 (Renal Fluid Electrolyte Physiol. 30): F420-F426, 1991]claimed that T3 increases to a similar degree both Na(+)-Pi symport and Na(+)-SO4 symport in murine renal BBM. Adult male rats were fed either normal (0.7% Pi; NPD) or high-phosphate (1.4% Pi; HPD) diet and received T3 (0.2 mg/100 g body wt ip) for 3 days before the kidneys were removed, BBMV were prepared, and the transport rates were determined. Although the Na(+)-Pi symport significantly increased (delta = +35%) in both NPD and HPD rats treated with T3, the Na(+)-35SO4 symport and Na(+)-D-[3H]glucose symports were not influenced by T3. Furthermore, treatment of NPD-fed mice with T3 using a similar protocol as rats resulted in a significant increase (delta = +26%) of Na(+)-(Pi)4 symport, but did not alter Na(+)-SO4 symport or Na(+)-glucose symport. Our findings thus document that T3 regulates selectively the Na(+)-Pi symporter in BBM without having any effect on other major divalent anions, such as SO4.

Animals↗
PubMed1993

Equilibrium and transient kinetic studies of the binding of cytochalasin B to the L-arabinose-H+ symport protein of Escherichia coli. Determination of the sugar binding specificity of the L-arabinose-H+ symporter.

The kinetics of the binding of cytochalasin B to the L-arabinose-H+ symport protein of Escherichia coli have been investigated, using a strain that over-produces the symport protein in the cytoplasmic membrane. Equilibrium binding studies revealed a single set of binding sites (2.9-8.9 nmol/mg protein) with a Kd of 0.7-1.0 microM at 22 degrees C. It proved possible to follow the transient kinetics of cytochalasin B binding by measuring the changes in the fluorescence of the L-arabinose-H+ symporter upon binding the ligand, by stopped-flow fluorescence spectroscopy. The association and dissociation rate constants thus determined were confirmed by rapid filtration measurements, using [3H]cytochalasin B, yielding values of 4.5-6.5 microM-1.s-1 and 4-5 s-1, respectively, consistent with Kd values obtained by measuring equilibrium binding of [3H]cytochalasin B by dialysis at 22 degrees C. Titration of the protein fluorescence with cytochalasin B yielded a similar binding site concentration and Kd value to those obtained in equilibrium binding studies. All the measurements of binding site concentration are consistent with a stoichiometry of 1 mol cytochalasin B binding sites/mol L-arabinose-H+ symport protein. Inhibition of both the rate and equilibrium binding of cytochalasin B by sugars indicated the following order of substrate binding 5-thio-D-glucose > D-fucose > L-arabinose > 6-deoxy-6-fluoro-D-galactose > D-xylose approximately 6-deoxy-D-glucose > D-galactose > D-glucose > D-ribose. Neither D-arabinose nor L-fucose had any significant inhibitory effect upon cytochalasin B binding.

Arabinose↗
PubMed1994

Proton and charge circulation through substrate symports in Saccharomyces cerevisiae: non-classical behaviour of the cytosine symport.

A yeast strain lacking cytosine deaminase activity and over-expressing the cytosine proton symport has been used to study three aspects of symport function. (1) The proton flow during cytosine uptake after depletion of cellular ATP implies that the distribution of cytosine eventually approaches equilibrium with the proton gradient, one proton being absorbed with each molecule of cytosine. After correction for the presence of a minor leak pathway for cytosine, the cytosine distribution during energy metabolism was used to assay the magnitude of delta microH. Values of about 280 mV at pH 5 were obtained in this way. (2) Certain other substrates of the cytosine symport (hypoxanthine and especially fluorocytosine) cause the uptake of more than one equivalent of protons, but nevertheless accumulate to the same extent as cytosine. This phenomenon appears to be distinct from that of proton slip and is termed pseudochannelling. (3) The recycling of symported protons through the proton pump is an ill-defined process in plants and fungi. It usually occurs only after a distinct time lag during which the change in bulk intracellular pH may be relatively small. We have found conditions where there is no apparent time lag before protons entering yeast with glycine or histidine are recycled. This behaviour is discussed in relation to the possible voltage characteristics of the proton pump, its putative regulation by delta microH and the metabolic consequences of ATP hydrolysis being accelerated.

Adenosine Triphosphate↗
PubMed1995

Subcellular localization of the inducible Chlorella HUP1 monosaccharide-H+ symporter and cloning of a Co-induced galactose-H+ symporter.

The unicellular green alga Chlorella kessleri can induce monosaccharide-H+ symport catalyzing the energy-dependent transport of D-glucose (D-Glc) and several other pentoses and hexoses across the plasmalemma. The gene coding for the inducible HUP1 monosaccharide-H+ symporter has been cloned and the protein has been characterized previously. The data presented in this paper demonstrate that the presence of the HUP1 gene product alone is not sufficient to cover the broad substrate specificity of monosaccharide transport in induced Chlorella cells. Two other HUP genes are shown to be co-induced in Chlorella in response to D-Glc in the medium. The cloning of HUP2 and HUP3 cDNA and genomic sequences is described, both being very homologous to HUP1. Modification of the 5' untranslated sequences of full-length cDNA clones of HUP2 and HUP3 allowed the functional expression of both transporters in Schizosaccharomyces pombe. HUP2 was shown to be a galactose-H+ symporter, whereas the substrate specificity of the HUP3 gene product is very similar to that of the HUP1 protein. However, HUP3 does not seem to be induced to high levels in Glc-treated Chlorella cells. Results are also presented proving that the product of the HUP1 gene is localized in the plasmalemma of D-Glc-induced Chlorella cells and is absent in plasma membranes of noninduced cells. Incubation of thin sections of Chlorella cells with anti-HUP1 antibodies and a fluorescence-labeled, second antibody yielded a ring of fluorescence on the surface of Glc-induced Chlorella cells.

Base Sequence↗
PubMed2004

Lack of correlation for sodium iodide symporter mRNA and protein expression and analysis of sodium iodide symporter promoter methylation in benign cold thyroid nodules.

Cold thyroid nodules (CTNs) are characterized by a reduced iodide uptake in comparison to normal thyroid tissue. The sodium iodide symporter (NIS) is the first step in thyroid hormone synthesis and mediates the active iodide transport in the thyroid cells suggesting that decreased iodide uptake could be a result of changes in NIS expression or molecular defects in the NIS gene. In contrast to previous studies, an intraindividual comparison of NIS mRNA expression in CTNs and their corresponding surrounding tissue was performed using direct detection of NIS mRNA. A significant reduction in NIS mRNA expression was detected in 86% of the 14 investigated CTNs. We hypothesized that human sodium iodide symporter (hNIS) transcriptional failure could be caused by primary molecular NIS gene defects and/or methylation of DNA in the NIS promoter. However, no mutation in the NIS cDNA nor in the NIS promoter region upstream up to-443 bp from the ATG start codon was detected. Therefore, primary molecular NIS gene defects were excluded. However, in 50% of CTNs with reduced NIS mRNA expression, the promoter region was hypermethylated. NIS mRNA expression in these hypermethylated CTNs only reached a maximum of 30% of the corresponding surrounding tissue. Hence, methylation of CpG islands in the NIS promotor could be a regulatory mechanism of NIS transcription in CTNs. Immunoblot revealed absent hNIS protein expression in the total cell membrane fraction in 45% of investigated nodules. In the majority of the remaining CTNs NIS protein expression was decreased in the nodule tissue compared to the corresponding surrounding tissue. For investigating protein expression immunhistochemistry has two advantages. First, the whole nodule area can be investigated, and second, NIS expression can be detected in areas where an immunoblot of a cell membrane fraction is negative. Interestingly, immunhistochemistry revealed higher NIS expression in 50% of CTNs compared to their corresponding surrounding tissues and NIS staining was predominantly intracellular. These data demonstrate that NIS protein expression does not reflect NIS mRNA expression. Therefore, factors that affect targeting of NIS to the plasma membrane are likely to be affected.

Blotting, Western↗
PubMed1997

Retinoic acid increases sodium/iodide symporter mRNA levels in human thyroid cancer cell lines and suppresses expression of functional symporter in nontransformed FRTL-5 rat thyroid cells.

Decreased iodide uptake in de-differentiated thyroid carcinomas impedes radioiodide therapy. RTPCR analysis revealed reduced expression of Na+/I- symporter (NIS) mRNA in human thyroid carcinomas as compared to normal thyroid. However, in follicular thyroid carcinoma cell lines FTC-133 and FTC-238, treatment with 1 microM all-trans retinoic acid (RA) markedly increased NIS mRNA levels. Anaplastic thyroid carcinoma cell lines HTh74 and C643 showed basal expression of NIS mRNA, but no RA-stimulation. All four cell lines contained the approximately 80 kD NIS protein as judged by Western blot, although they did not accumulate iodide. In contrast, in nontransformed rat FRTL-5 cells, 1 microM RA downregulated NIS mRNA levels, inhibited the TSH- or forskolin-triggered induction of NIS message after TSH-depletion, and reduced iodide uptake to 38% after 5 d. This divergent RA-responsivity of NIS may provide the means to target radioiodide to thyroid carcinomas by upregulating iodide transport into tumor tissue while simultaneously inhibiting iodide accumulation in normal thyrocytes and may thus re-establish the potential for radioiodide therapy.

Animals↗
PubMed2003

The rat sodium iodide symporter gene permits more effective radioisotope concentration than the human sodium iodide symporter gene in human and rodent cancer cells.

Expression of the sodium iodide symporter (NIS) gene in tumor cells may provide a novel mechanism for treating cancer. The NIS mediates the normal physiological transport of iodide across the thyroid cell membrane. This mechanism of iodide uptake has been used to both diagnose and treat thyroid cancer. Tissue expression of the NIS is largely limited to the thyroid; therefore, expression of the NIS gene in cancer cells would allow for specific iodine uptake, radioisotope accumulation, and treatment. In this study, we directly compared the human and rat NIS (rNIS) for their ability to concentrate radioisotope into human and rodent cancer cells. Perchlorate-sensitive (125)I uptake in multiple cell lines was demonstrated following transduction with retroviral vectors expressing either the human or rNIS gene. Surprisingly, iodine uptake was consistently higher with the rNIS gene, up to 5-fold greater, when compared to the human gene, even within a variety of human tumor cell lines. This iodine uptake allowed for cell killing following (131)I treatment in NIS-transduced cells when assayed by in vitro clonogenic assays. These results demonstrate that the rNIS gene provides superior iodine uptake ability, and may be preferable for use in designing anticancer gene therapy approaches.

Animals↗
PubMed2005

Cell surface targeting accounts for the difference in iodide uptake activity between human Na+/I- symporter and rat Na+/I- symporter.

CONTEXT: The Na+/I- symporter (NIS) has been proposed to serve as an imaging reporter gene to optimize vector delivery, monitor therapeutic gene expression, and map the tissue/organ sites of repopulated progenitor cells in vivo. In addition, NIS can serve as a therapeutic gene to facilitate targeted radionuclide therapy for various cancers. OBJECTIVE: It was reported that rat NIS (rNIS) confers higher radioactive iodide uptake (RAIU) activity than human NIS (hNIS). We aim to investigate the mechanism underlying this difference. RESULTS: We showed that the open reading frames (ORF) of hNIS and rNIS, although encoding for proteins with 83% amino acid identity, exhibit a significant difference in RAIU activity in transfected cells. The ORF rNIS confers four to five times higher RAIU activity as well as cell surface NIS accumulation than ORF hNIS despite similar total NIS protein levels. Multiple regions appear to play roles in the difference in NIS cell surface levels between ORF hNIS and ORF rNIS, indicating that proper folding of NIS in tertiary structure is critical for NIS cell surface targeting. We also showed that the kinetics of Na+ binding are different between ORF hNIS and ORF rNIS, and that site-directed mutation changing Ser200 to other uncharged amino acid significantly increased RAIU activity in ORF hNIS. CONCLUSIONS: NIS transgene could be optimized for cell surface trafficking and RAIU activity to improve its clinical applications.

Amino Acid Sequence↗
PubMed2006

Correlation of Na+/I- symporter expression and activity: implications of Na+/I- symporter as an imaging reporter gene.

UNLABELLED: The Na(+)/I(-) symporter (NIS) has been proposed as an imaging reporter gene to ascertain the expression of therapeutic genes in targeted tissues. In this study, we investigated whether posttranslational processing and cell-surface trafficking of NIS affect NIS-mediated radioiodide uptake in cells expressing exogenous NIS. METHODS: We established FTC133, HeLa, and PC12 cell lines with doxycycline-inducible NIS expression to investigate the correlation among total NIS protein levels, cell-surface NIS protein levels, and NIS-mediated radioiodide uptake in cells induced with various levels of NIS. RESULTS: We found that most exogenous NIS proteins were efficiently trafficked to the cell surface; thus, a possible deficiency in NIS cell-surface trafficking is not a concern for clinical applications of NIS gene transfer. The extent of radioiodide uptake correlated with cell-surface NIS protein level within a certain range, suggesting that the imaging signals can quantify levels of NIS expression only within a certain range in vivo. Finally, a moderate increase in NIS protein level significantly increased radioiodide uptake, indicating that a low level of NIS expression is sufficient to facilitate radionuclide imaging in vivo. CONCLUSION: Our study suggests that NIS will be useful as an imaging reporter gene to ascertain that the therapeutic gene is localized to the correct tissue and to monitor the expression levels and duration of the therapeutic gene.

Cell Line, Tumor↗
PubMed1990

Mechanism of Na+/proline symport in Escherichia coli: reappraisal of the effect of cation binding to the Na+/proline symport carrier.

The proton and sodium ion dependences of the proline binding and transport activities of the proline carrier in Escherichia coli were investigated in detail. The binding activity in cytoplasmic membrane vesicles from a carrier over-producing strain (PT21/pTMP5) was absolutely dependent on the presence of Na+, but did not necessarily require protonation of the carrier, in contrast to the model previously reported (Mogi, T., Anraku, Y. 1984. J. Biol. Chem. 259:7797-7801). Based on this and previous observations, we propose a modified model of the proline binding reaction of the proline carrier, in which a proton is supposed to be a regulatory factor for the binding activity. The apparent Michaelis constant of proline (Kt) of the transport activity of cytoplasmic membrane vesicles from the wild type E. coli strain driven by a respiratory substrate, ascorbate, showed dependence on a low concentration of sodium ion. The Michaelis constant of sodium ion for transport (KtNa) was estimated to be 25 microM. The proline transport activities in membrane vesicles and intact cells were modulated by H+ concentration, the inhibitory effect of protons (pKa approximately equal to 6) being similar to that observed previously (Mogi, T., Anraku, Y. 1984. J. Biol. Chem. 259:7802-7806). Based on these observations and the modified model of substrate binding to the proline carrier, a model of the proline/Na+ symport mechanism is proposed, in which a proton is postulated to be a regulatory factor of the transport activity.

Amino Acid Transport Systems, Neutral↗
PubMed2001

Differential regulation of the human sodium/iodide symporter gene promoter in papillary thyroid carcinoma cell lines and normal thyroid cells.

The absence of TSH-stimulated radioiodide uptake in differentiated thyroid cancer is associated with a high recurrence rate and reduced survival. We studied regulation of the sodium/iodide symporter gene in human papillary thyroid cancer cell lines (BHP) and primary human thyroid cells. BHP cells expressed very low levels of sodium/iodide symporter mRNA and did not concentrate iodide, but iodide uptake was restored to levels seen in FRTL-5 rat thyroid cells by stable transfection of a sodium/iodide symporter cDNA. Sodium/iodide symporter gene expression, therefore, was necessary and sufficient for iodide uptake in BHP cells. We cloned the human sodium/iodide symporter gene 5'-flanking region and analyzed progressive 5'-deletions in transient transfections. We identified a region, -596 to -268, essential to confer full promoter activity in primary normal human thyroid cells. Sodium/iodide symporter promoter activity in four BHP cell lines, however, was markedly reduced, consistent with down-regulation of the endogenous sodium/iodide symporter gene. Nuclear extracts from BHP 2-7 cells had reduced or absent binding to regions of the sodium/iodide symporter promoter shown to be critical for expression, compared with nuclear extracts from FRTL-5 cells. Competition studies indicated that these nuclear proteins were not known thyroid transcription factors. Modifications of the sodium/iodide symporter promoter with demethylation or histone acetylation did not increase sodium/iodide symporter expression, and no deletions of the critical regulatory region were identified in the endogenous gene in BHP cells. Regulation of the sodium/iodide symporter 5'-flanking region in transient transfection paralleled endogenous sodium/iodide symporter expression. Reduced expression of potential novel nuclear factor(s) in these cell lines may contribute to reduced sodium/iodide symporter expression resulting in absence of iodide uptake in some papillary thyroid cancers.

Base Sequence↗
PubMed2000

Apical Na+-Cl- symport in rabbit gallbladder epithelium: a thiazide-sensitive cotransporter (TSC).

Cl- apically enters the epithelium of rabbit gallbladder by a Na+-Cl- symport, sensitive to hydrochlorothiazide (HCTZ). Since HCTZ also activates an apical SITS-sensitive Cl- conductance (G(Cl)), the symport inhibition might be merely due to a short circuit of the symport by G(Cl) rather than to a direct action of HCTZ on the symporter. To examine whether the symport is directly inhibited by HCTZ and whether the symporter belongs to the family of thiazide-sensitive cotransporters (TSC), radiochemical measurements of the apical Cl- uptake, electrophysiological determinations of intracellular Cl- and Na+ activities (a(i,Cl) and a(i,Na)) with selective theta microelectrodes and molecular biology methods were used. The 13Cl- uptake proved to be a measurement of the apical unidirectional Cl- influx (Jmc) and of the symport only (without backflux components), with measuring times of 45 sec under all experiment conditions; its inhibition by HCTZ was unaffected by G(Cl) activation or abolition. After HCTZ treatment the decrease in a(i,Cl) (measured as the initial rate or in 3 min) was larger than the decrease in a(i,Na). The difference was reduced to one third in a group of epithelia in which the elicited G(Cl) was reduced to one third; moreover it was abolished in any case when G(Cl) was abolished with 10(-4) M SITS. The SITS-insensitive rate of a(i,Cl) decrease was equal to that of the a(i,Na) decrease in any case. Thus the a(i,Cl) decrease displays a component dependent on G(Cl) activation and a second component dependent on symport inhibition. Using the RT-PCR technique a cDNA fragment was obtained that was 99% identical to the corresponding region of the rabbit renal TSC isoform. The results indicate that in rabbit gallbladder epithelium HCTZ displays a dual action, namely G(Cl) activation and Na+-Cl- symport inhibition. This Na+-Cl- symporter is the first TSC found to be functionally expressed in a nonrenal or nonrenal-like epithelium.

Amino Acid Sequence↗
PubMed1995

A novel proline, glycine: K+ symporter in midgut brush-border membrane vesicles from larval Manduca sexta.

Alkali-cation-dependent uptake of proline and glycine into brush-border membrane vesicles from the midgut of the larval tobacco hornworm Manduca sexta was investigated using rapid filtration assays. Uptake of both amino acids was by electrophoretic symport, with K+ being the favored cation at pH 10. Counterflow accumulation of proline was elicited by glycine and vice versa, suggesting that the two amino acids are transported by a common symporter, which we designate the pro, gly: K+ symporter. L-alpha-Aminoisobutyric acid was the only other amino acid that elicited the accumulation of both proline and glycine. D-Proline was not symported; L-proline, glycine and L-alpha-aminoisobutyric acid appear to be the only substrates of the pro, gly: K+ symporter. Neutral amino acids with relatively short sidechains elicit glycine accumulation, suggesting that glycine may also be symported by the well-established neutral amino acid system. Since proline does not utilize the broad-spectrum, neutral system, its symport appears to be exclusively through the pro, gly: K+ symporter. Proline symport was found mainly in posterior midgut vesicles, suggesting that the pro, gly: K+ symporter may be localized in this region of the midgut.

Animals↗
PubMed1994

Na(+)-I- symport activity is present in membrane vesicles from thyrotropin-deprived non-I(-)-transporting cultured thyroid cells.

The active accumulation of I- in the thyroid gland is mediated by the Na(+)-I- symporter and driven by the Na+ gradient generated by the Na+/K(+)-ATPase. Thyrotropin (TSH) stimulates thyroidal I- accumulation. Rat thyroid-derived FRTL-5 cells require TSH to accumulate I-. TSH withdrawal for over 7 days results in complete loss of Na(+)-I-symport activity in these cells [Weiss, S. J., Philp, N. J. and Grollman, E. F. (1984) Endocrinology 114, 1090-1098]. Surprisingly, membrane vesicles prepared from FRTL-5 cells maintained in TSH-free medium [TSH(-)cells]accumulate I-, suggesting that the absence of Na(+)-I- symport activity in TSH(-) cells cannot be due solely to a decrease in the biosynthesis of either the symporter or a putative activating factor. This finding indicates that the Na(+)-I- symporter is present, probably in an inactive state, in TSH(-) cells despite their lack of Na(+)-I- symport activity. Na(+)-I- symport activity in thyroid membrane vesicles is enhanced when conditions for vesicle preparation favor proteolysis. Subcellular fractionation studies in both TSH(+) and TSH(-) cells show that Na(+)-I- symport activity is mostly associated with fractions enriched in plasma membrane rather than in intracellular membranes, suggesting that the Na(+)-I- symporter may constitutively reside in the plasma membrane and may be activated by TSH.

Animals↗
PubMed1997

[The effect of NaK2Cl symport and chloride channel permeability on ion flux balance and on transmembrane ion distribution in different types of animal cells].

The relationships between monovalent ion fluxes via major cell membrane pathways (Na/K pump, NaK2Cl symporter, electroconductive sodium, potassium and chloride channels) and steady state transmembrane ion distribution, membrane potential and cell water content were calculated for the high potassium animal cells with high and low membrane potential. It is found that variation in NaK2Cl symport or chloride electroconductive permeability causing changes in cell water content of high magnitude do not lead to significant changes in the intracellular Na/K ratio or membrane potential, in contrast to the effects caused by variation in the Na/K pump fluxes or permeability of the Na and K channels. It is shown that water content in cells with a high membrane potential, e.g. of about 70 mV, cannot be increased due to an increase in NaK2Cl symport by more than 1.6 times. In cells with a low membrane potential an increase in symport leads to a decrease in water content, which is also limited. In cells with membrane potential of about 10 mV the water content cannot be decreased more than by 1.8 times. When NaK2Cl symporter is operating, the effect of chloride channel permeability on the ion and water balance is quite opposite to the symport and is limited by the same boundaries. It is shown that effects caused by changes in symport and in chloride permeability can be differentiated only by the analysis of kinetic (fluxes, transport rate constants etc.) but not "static" characteristics of ion distribution. It is shown that under some circumstances the influence of NaK2Cl symport and chloride channel permeability on ion and water balance can be strong even at a very small symport share in the overall flux.

Animals↗
PubMed1989

Increased Na+-taurine symporter in rat renal brush border membranes: preformed or newly synthesized?

The renal adaptive response to a varied intake of sulfur amino acids is demonstrated by an increase in the initial rate of Na+-taurine symport (cotransport) by rat renal brush border membrane vesicles (BBMVs) after 8-14 days of a low methionine diet. A high (3%) taurine diet reduces Na+-taurine symport. Fasting for 3 days, which depletes renal tubule cell taurine content, also enhances Na+-taurine symport both initially (15 s) and throughout the overshoot. In this study we examine the possibility that a rapid-onset adaptive response is expressed in BBMV, with the increased Na+-taurine symport reflecting the incorporation of preformed symporter into membranes rather than new synthesis. Rats fed the low methionine diet for 14 days were placed on the high taurine diet for 12-18 h; Na+-taurine symport activity fell by 40%. Fasting for 4 h restored low methionine diet levels of Na+-taurine symport activity (92 pmol.mg protein-1.15 s-1), defining a rapidly induced rise in uptake. Colchicine (0.6 mg) was injected prior to fasting in a group of rats because it blocks the incorporation (import) of preformed symporter into the membrane. Animals injected with colchicine had a pattern of BBMV uptake similar to that found in animals switched to the high taurine diet for 18 h. This agent blocked the rapidly induced rise in uptake. Feeding with the high taurine diet for 4 h caused a fall in uptake of 16.5%; colchicine blocked this reduction in uptake. These results indicate that the nephron can respond rapidly to changes in the intake of amino acids, conserving taurine in periods of nutrient lack and excreting excess taurine within 4 h in periods of surfeit. This rapid response is expressed at the brush border surface. The use of cholchicine indicates that the increase or reduction in Na+-taurine symport activity is due to incorporation (import) of transporter into the BBMV rather than to de novo synthesis.

Amino Acids, Sulfur↗