Changes of renal taurine transport after treatment with triiodothyronine or dexamethasone in amino acid loaded rats

Exp Toxic Pathol 1998; 50: 432-439 Gustav Fischer Verlag

Institute of Pharmacology and Toxicology, Friedrich Schiller University of lena, Germany

Changes of renal taurine transport after treatment with triiodothyronine or dexamethasone in amino acid loaded rats* CH. FLECK and BEATE LANGNER With 5 figures and 2 tables

Address for correspondence: Prof. Dr. CH. FLECK, Klinikum der Friedrich-Schiller-Universitat lena, Institut fUr Pharmakologie und Toxikologie, D - 07740 lena, Germany; Tel.: ++49 +3641 +938720, Fax: ++49 +3641 +93 8702, E-mail:

Key words: Taurine transport, renal; Kidney, taurine transport; Renal taurine transport; Triiodothyronine; dexamethasone.

Summary In adult female anaesthetized rats, the influence of triiodothyronine or dexamethasone on renal amino acid (AA) handling was investigated in taurine (45 mg/lOO g b.wt.) loaded animals. Bolus injections of taurine were followed by temporary increase in fractional excretion (FE AA ) of taurine as well of the endogenous amino acids which were not administered. Under taurine load conditions, triiodothyronine treatment (20 Ilg/100 g b.wt. for 3 days, i.p. once daily) was followed by a slight stimulation of the renal taurine reabsorption: the increase in FEtaurine after taurine load was lower than in untreated rats. Dexamethasone (60 Ilg/100 g b.wt. for 3 days, i.p. once daily) was without significant effect on FEtaurine in taurine loaded rats. In non taurine loaded rats there was no hormone influence at all. Similarities and differences between the effects of bolus injections of taurine, glutamine, and leucine on the FEAA of these three amino acids were compared in detail to further clarify the reason for the increased amino acid reabsorption capacity after pretreatment with triiodothyronine or dexamethasone.

Introduction Only little information exists in the literature describing hormonal control of renal amino acid handling. For example, testosterone was shown to stimulate amino acid uptake in murine renal cortical slices (KOENIG et al. 1982), parathyroid hormone increases amino acid excretion by inhibition of amino acid reabsorption (SCRIVER and BERGERON 1974), and dexamethasone stimulates taurine trans-

* Dedicated to Prof. Dr. WOLFGANG KLINGER on occasion of his 65th birthday on July 3, 1998. 432

Exp Toxic Pathol50 (1998) 4-6

port in flounder renal tubules (KING et al. 1982). In own experiments (FLECK 1992), repeated administration of triiodothyronine (T3), dexamethasone or epidermal growth factor (FLECK and PERTSCH 1998) caused significant changes of fractional amino acid excretion (FEAA ): In young animals the fractional excretion of endogenous amino acids was reduced after dexamethasone and T3 treatment, indicating stimulatory effects of both hormones on tubular amino acid carrier systems in immature animals. In adult rats, the stimulatory effects of hormone treatment could be found only after administration of an amino acid load exhausting renal amino acid reabsorption capacity (FLECK et al. 1997). In the present study, the renal handling of taurine was investigated after administration ofT3 or dexamethasone. In mammals, taurine, 2-aminoethane sulfonic acid, is one of the most abundant of the low-molecular-weight organic constituents. The phylogenetic ally oldest function for taurine, next to bile salt synthesis, is that of osmoregulation (UCHIDA et al. 1992). The nonessential ~-amino acid taurine is inert in renal tissue (FRIEDMAN et al. 1983). It is one of the end products of sulfur metabolism in animals. Taurine was chosen for our experiments for the following reasons: • Taurine, although not an amino acid sensu strictori, is transported by ~-amino acid carriers (ZELIKOVIC and CHESNEY 1989). Nevertheless, its renal handling is different from those of the other amino acids (SILBERNAGL et al. 1997). • The fractional excretion of taurine is relatively high compared to the other amino acids (JEAN et al. 1984; CHESNEY et al. 1987). Therefore, the comparison of renal taurine transport with those of the other amino acids like glutamine and leucine (see FLECK et al. 1997) could further characterize the regulatory functions of

T3 and dexamethasone concerning renal amino acid handling. • Taurine is a substance involved in a couple of actions within the organism (for review see HUXTABLE 1992), therefore its toxicity should be very low and it can be administered in high doses. Furthermore, the distribution of taurine is ubiquitous and the concentrations are high, especially in platelets, electrically excitable tissues, and secretory structures; concentrations are low in extracellular fluids.

lyzed by HPLC on an amino acid analyzer (Knauer, Berlin, Germany) with o-phthalaldehyde as a fluorescent amino ligand. Statistics: The results are summarized as means ± S.E.M. with n = 6 in each group. The level of significance for differences between the observations was assessed with the Mann-Whitney-Wilcoxon-test and considered statistically significant when p ~ 0.05 (FE AA ) and p ~ 0.001 (plasma concentrations), respectively.

Results Material and methods Animals: Investigations were performed on female Wistar rats (Han:Wist) of our institute's own out-bred stock. At the beginning ofthe experiments the animals were 2 months old and the average body weight was 162 ± 6 g. The rats were kept under standardized conditions including standard AItromin 1316 diet and free access to tap water. Experimental design: The rats were anaesthetized with ketamine (Ursotamin° Serumwerk Bernburg, Germany, 7.5 mg/lOO g b.wt.) and xylazine (Ursonarkon° Serumwerk Bernburg, Germany, 1.2 mgllOO g b.wt.). Both substances were administered intramuscularly. A catheter was placed in a tail vein. The animals were then infused isotonic saline containing 4 gil fluorescein isothiocyanate (FITC)-inulin (Bioflor, Uppsala, Sweden) at a rate of 4 mlll00 g b. wt. per hour. Thereafter a polyethylene catheter was inserted into the urinary bladder. Urine was collected in 20-minute intervals over a time of 3 hours. In the middle of each period and at the end of the experiment blood was collected from the retrobulbar plexus. Glomerular filtration rate (GFR) was determined by inulin clearance. Inulin concentration was measured spectrofluorometrically using FITC-inulin (SOHTELL et al. 1983). Amino acid load: Rats were loaded with 45 mgll 00 g b.wt. taurine (SIGMA, St. Louis, U.S.A.) dissolved in 2 ml normal saline per 100 g b. wt. The injection solution of taurine had an osmolarity of 365 mosmol and a pH of 6.43. Taurine was administered as a bolus injection intravenously at the beginning of the clearance experiment. Control animals received the same volume of normal saline. Hormone treatment: Triiodothyronine (T3; SIGMA, St. Louis, U.S.A.) was administered intraperitoneally in doses of 20 Ilgl100 g b.wt. once daily for 3 days. Dexamethasone (Dexa; Fortecortin° Mono, E. Merck, Darmstadt, Germany): 60 Ilg/100 g b.wt. were given i.p. for 3 days, once daily. Both substances were dissolved in normal saline (l mill 00 g b.wt.). Controls received the solvent only. Amino acid determination: The determination of amino acids by column chromatography with fluorescence detection is based on that developed by ROTH and HAMPA! (1973) and has been described in detail elsewhere (SILBERNAGL 1983). Briefly, proteins were removed from urine and plasma samples by administration of trichloroacetic acid. Then the samples were diluted with citrate buffer and ana-

As shown in figure I, after bolus injection of taurine both taurine plasma concentration and fractional excretion of taurine increased significantly immediately after load 7- and 3-fold, respectively, as a sign of overloading of renal taurine reabsorption capacity. Interestingly, FEtaurine was already 20 minutes after taurine load not longer different from control values whereas taurine plasma concentrations remained enhanced up to one hour after taurine administration. Under taurine load, the FEAA of the other endogenous amino acids were also influenced (table 1): the 5-fold increase in ~-alanine excretion after taurine was most impressive. In 8 of 16 amino acids the FEAA was slightly enhanced but it was diminished for glutamine and leucine significantly. Taurine bolus injection was without consequences on endogenous amino acid plasma concentrations during the clearance study. After pretreatment of rats with either T3 or dexamethasone, GFR was unchanged in controls and taurine loaded animals (0.92 mllmin x 100 g b.wt.). Nevertheless, after T3 pretreatment urine flow was slightly reduced in control rats without taurine bolus. On the other hand, in all experimental groups the diuretic effect of the taurine load could be demonstrated (table 2). In non taurine-loaded rats pretreatment with dexamethasone or T3 did not influence the FEtaurine, but repeated administration of T3 reduced taurine plasma concentration significantly (fig. 2, upper part). After administration of a taurine bolus injection, its plasma concentration increased about 7fold in non hormone treated (see also fig. I) and T3 or dexamethasone treated rats (fig. 2, lower part). 11/2 hours after taurine load, plasma levels of controls were reached in all three groups. Immediately after taurine administration, FEtaurine was significantly enhanced independently of hormone treatment. However, 30 min after load. FEtaurine was distinctly lower in T3 treated rats compared to loaded, non-hormone treated animals. FEtaurine remained lower in T3-rats and, to a lesser degree in dexamethasone treated rats, up to the end of the experiment. The increase in FEAA after taurine load, shown in table I, occurred also in T3 or dexamethasone treated rats (absolute values not shown), but relative raises in FEAA were significantly lower in hormone treated rats compared to non-hormone treated animals with the exception of arginine, tyrosine, and valine (fig. 3). Exp Toxic Pathol 50 (1998)

4~6

433

2000 L800 ., L600 , 1400 1200

•

p Lasma concentration controL taurine

•

..::.

.

~.

~ tOOO

I

800 600 400 200 0

I

• 30

0

60

9

:I ~

150

120

180

fractiona l excretion

8

"0

90

•

5 • 4

:j 0 0-20

20-40

60-90 90 - 120 40-60 time after bolus injection [min)

120 - 150

150 - ISO

Fig. 1. Influence of taurine bolus injection on taurine plasma concentration and its fractional excretion. Controls (homogenous band) received saline bolus only (2 mIl 100 g b. wt.). Arithmetic means ± S.E.M., n = 6-9. * - significantly different from saline group with P ~ 0.05 (FE AA ) and 0.001 (plasma concentration), respectively.

Table 1. Plasma concentrations and fractional excretion of endogenous amino acids (AA) in controls (NaCl) and after taurine bolus injection. Arithmetic means ± S.E.M.; n = 4-6. *- significant differences between taurine bolus and control (plasma concentration: p ~ 0,001; FEAA : p ~ 0,05). AA

acidic AA Asp Glu

plasma concentration [flM]

fractional excretion

NaCI

taurine

NaCI

taurine

19 ± 2 221 ± 30

5.62 ± 0.09 3.79 ± 0.72

7.14 ± 1.76 1.97 ± l.00

46 ± 6 84 ± 12

[%]

basic AA Arg Lys

133±2 198 ± 9

140 ± 12 198 ± 10

0.59 ± 0.13 0.35 ± 0.03

1.42 ± 0.18 0.30 ± 0.04

neutralAA Ala Asn GIn Gly Leu Phe Ser Thr Tyr Val

203 ± 17 56 ± 1 283 ± 8 127 ± 1 128 ± 15 62 ± 8 174 ±2 429 ± 26 62 ± 13 196 ± 20

250 ± 28 53 ± 3 463 ± 32 126 ± 8 177 ± 7 99 ± 13 166 ± 15 535 ± 21 59 ±2 234 ±7

1.14 ± 0.26 1.35 ± 0.30 0.83 ± 0.01 2.09 ± 0.39 0.66 ± 0.11 0.66 ± 0.10 1.54 ± 0.35 0.35 ± 0.13 1.44 ± 0.21 0.47 ± 0.08

1.29 ± 0.28 1.19 ± 0.26 *0.39 ± 0.05 2.68 ± 0.89 *0.22 ± 0.04 0.37 ± 0.10 1.07 ± 0.24 0.72 ± 0.10 1.51 ± 0.25 0.33 ± 0.05

6±1 *1767±50

4.91 ± 0.67 2.46 ± 0.46

*26.09 ± 5.10 *7.l4±l.00

other ~-Ala

Tau

434

9±1 101 ± 1

Exp Toxic Pathol 50 (1998) 4-6

Table 2. Urine volume and GFR after treatment with dexamethasone (Dexa) or triiodothyronine (T3) in taurine loaded rats. Comparison with rats receiving NaCl bolus instead of taurine at the beginning of the clearance experiment. Arithmetic means ± S.E.M.; n = 6-9. * - significant difference between taurine load and NaCl bolus (p ~ 0.05); ** - significant effect of hormone treatment (p ~ 0.05). group

urine volume [mIll 00 g b.wt.]

GFR

0-20 min

0-180 min

[ml/(min x 100 g b.wt.)]

1.3 ± 0.1 0.8 ± 0.2 0.5 ± 0.1 **

4.8 ± 0.5 2.8 ± 0.6 2.7 ±0.9

0.92 ± 0.03 0.78 ± 0.04 0.76 ± 0.04

NaCI bolus NaCI-treatment Dexa T3 taurine bolus NaCI-treatment Dexa T3

180

* * *

1.6 ± 0.1 1.5 ± 0.3 1.4 ± 0.1

2:

0.96 ± 0.05 1.00 ± 0.05 0.93 ± 0.05

*

3,5

fractional e cretion

plasma concentration

ISO •

3,0

120

2,5

~

90 . 60 ;

~

5.0 ±0.6 7.2 ± 1.0 4.4 ± 0.8

2,0 '0 1,5 e-

#

1,0 0,5

0 Co 2000 _ 1500 -

!

Oexa

•

1'3

0,0

Co

Oexa

T3

plasma concentration

•

1000 _ 500 0 0

30

12

Fig.2. Influence of a treatment with dexamethasone or triiodothyronine on taurine plasma concentration and its fractional excretion without (upper part) and with (lower part) taurine bolus injection. Controls (homogenous band) received saline bolus only (2 mIll 00 g b. wt.). Arithmetic means ± S.E.M., n =6-9. * - significantly different from saline group and # - significant hormone effect with p ~ 0.05 (FEAA ) and p ~ 0.001 (plasma concentration), respectively.

60

90

120

fractional excretion

10 control taurine 8

dexamethasone taurine lriiodthyronine taurine

'0

e-

6

_

4

control aO

--~~--------------------------.

•

2

o

I 0·20

20 -40 40 ·60 time after bolus injection (min I

90 -120

Exp Toxic Pathol 50 (1998) 4-6

435

4,5

dexamethasone

4,0

fractional excretion

3.5

0,5 0,0

Asp Glu

Arg Lys

Ala Asn Gn G1y Leu Phe Ser Thr Trp Tyr

basic

acidic

18

14

. glutamine

f'I

.

11

-

6 4

1 I

-

,.....,

1-

1-

~

I

o taurine

. . -

.

8

0

IJ leucine

.

10

0

.

#

-

'#

~

[

:=

C

IJ

I

control

de'Cametha on

In previous studies (FLECK et al. 1997) similar experiments have been performed using glutamine (45 mg/1 00 g b.wt.) or leucine (20 mg/100 g b.wt.) as bolus amino acids. In figure 4, the different influences of T3 and dexamethasone on the FElaurine are compared: Surprisingly, in controls without hormone treatment the increase in FElaurine was the highest after leucine administration and not after taurine bolus. However, considering the relatively large standard errors, the increases in FElaurine were quite comparable after the three types of amino acid load (about 3-5fold). Dexamethasone treatment was without effect on FElaurine independently of the kind of bolus amino acid whereas T3 treatment diminished the increase in FElaurine in all three cases, after glutamine and leucine bolus even significantly. In figure 5, the three kinds of amino acid load were compared concerning their effects on their own FEAA in non-hormone treated and T3 or dexamethasone treated rats. It could be shown that the hormone effects on renal handling of amino acids depend on the respective bolus amino acid, the FEAA of which is significantly enhanced under load conditions: Taurine: dexamethasone was without effect on FElaurine whereas T3 improved taurine reabsorption at least in the second clearance period (30-60 min). Leucine: both T3 and dexamethasone pre436

"lr-'Ai\

fractional excretion

16

0"

B- la

al

neutral

Fig.3. Influence of a treatment with dexamethasone or triiodothyronine on the fractional excretions of endogenous amino acids in taurine loaded rats. Arithmetic means, n =6-9.

Exp Toxic Pathol 50 (1998) 4-6

r:

1

::::

triiodthyron ine

~

Fig.4. Comparison of the influences of a load with glutamine, leucine, and taurine, respectively, on the fractional excretion of taurine in controls and dexamethasone or triiodothyronine treated rats. Homogenous bands: Means ± S.E.M. of saline loaded rats. Arithmetic means ± S.E.M., n =6-9. * - significantly different from saline group (p ~ 0.05). # - significant hormone effect (p ~ 0.05).

vented the increase in FEleucine after leucine bolus injection. Glutamine: only immediately after glutamine administration (extremely high plasma concentrations) dexamethasone reduced significantly the FEglulamine, in the second clearance period the dexamethasone effect disappeared. T3 was without influence on renal glutamine transport.

Discussion

Taurine load Amino acids are reabsorbed from the tubular lumen by a saturable, carrier-mediated, concentrative transport mechanism driven by a Na+-electrochemical gradient across the luminal membrane. This process is followed by efflux mainly via carrier-mediated, Na+-independent facilitated diffusion across the basolateral membrane (CHESNEY et al. 1994). At least seven distinct, but largely interacting Na+dependent amino acid transport systems have been identified in renal brush border membrane (ZELIKOVIC and CHESNEY 1989). Taurine/~-alanine transporters were cloned from a mouse brain cDNA (LIU et al. 1992), from humal placental cDNA (RAMAMOORTHY et al. 1994), and from

12

fractional excretion 0- 30 min

10 •

8 0" 6 !...

2

o 12 30 - 60 min

Fig. 5. Influence of a bolus injection of taurine, leucine, and glutamine, respectively, on their own fractional excretion 0-30 min (upper part) and 30-60 min (lower part) after load in triiodothyronine or dexamethasone treated rats. Homogenous bands: Means ± S.E.M. of respective saline loaded rats. Arithmetic means ± S.E.M., n = 6-9. * - significantly different from saline group (p ~ 0.05). # - significant hormone effect (p ~ 0.05).

10

• control

8 Q

!...

o de'<3me thaso ne o triiodthyronine

6

o

taurine

human thyroid (JHIANG et al. 1993), which are highly homologous to that of the kidney. After taurine load, its plasma concentration increased significantly, even if an unusually high level of confidence (p ~ 0.001) is considered. This high level of confidence for the comparison of amino acid plasma concentrations was chosen because of the high interindividual variations (SILBERNAGL 1988). As shown previously for glutamine and leucine (FLECK et al. 1997), after bolus injection of taurine its FEAA increased significantly. Immediately after the administration of a volume load (2 mIl 100 g b.wt.), urine flow is significantly enhanced (not shown) . This effect, however, is quite similar in taurine and saline loaded rats and, therefore, it is without consequence for the comparisons between the different experimental groups. The administered bolus volume is nearly completely excreted within the first clearance period and hyperhydratation is avoided. Furthermore, glomerular filtration is unchanged after taurine load. This is in accordance with BREZIS et al. (1984) reporting unchanged GFR after taurine administration in isolated perfused kidneys. Bolus injection of taurine influenced the FEAA of the other endogenous amino acids, too. Similar findings have been obtained after e.g. glutamine or leucine bolus injection (FLECK et al. 1997). This is in accordance e.g. with TIETZE et al. (1992) describing the same for amino acid

leucine

glutamine

load in humans. The reason for this phenomenon could be a) a direct competition at the amino acid carrier sites in the kidney between taurine and endogenous amino acids (COLLARINI and OXENDER 1987), b) a loss of ATP and, therefore, a reduction of the Na+- gradient in the renal tubuli (GUTMANN et al. 1993) as a consequence of enhanced GFR and urine flow , and c) the reduced contact time in the nephron because of the increased urine flow. The mutual interaction between taurine and ~-alanine is most impressive and indicates competition phenomena at the ~-amino acid transporter (CHESNEY et al. 1985). Competition experiments revealed that taurine and ~­ alanine drastically reduced the uptake of one another by the high affinity sodium dependent transport system (JESSEN 1994). However, ~-amino acids could also compete with some a-amino acids, but with a low affinity (JESSEN et al. 1996). Nevertheless, this interaction explains the increase in FEAA of various endogenous amino acids after taurine bolus injection. Beside this competition, energy consumption in the proximal tubular cell could be enhanced under taurine load. Therefore, the energy supply for reabsorption of the other amino acids could be diminished. Similar findings were reported for p-aminohippurate: at high concentrations PAH reduces taurine uptake, possibly by competing for sodium ions (CHESNEY et al. 1985). Exp Toxic Pathol 50 (1998) 4- 6

437

Hormone treatment Treatment of the animals with T3 or dexamethasone, two catabolic hormones, caused different effects on renal taurine transport. In principle, urine flow is reduced after T3 and dexamethasone, especially in saline loaded rats. The glomerular filtration rate is not changed significantly, neither after T3 nor after dexamethasone administration and independently of amino acid load. This result confirms previous findings reporting only slight to moderate changes in urine flow and GFR after hormone pretreatment (BRAuNLICH 1984; BRAuNLICH et al. 1986). As mentioned in the introduction, a stimulation of amino acid transport can be expected only after employment of the transport capacity. In non amino acid loaded animals no effect of both T3 or dexamethasone could be found. But after taurine bolus injection the increase in FEtaurine is slightly lower in T3 treated animals whereas dexamethasone had no effect on renal taurine transport. This finding is in contrast to those found for glutamine or leucine load (FLECK et al. 1997): in these investigations it could be shown that three days administration of both T3 and dexamethasone significantly reduces FEleucine after leucine bolus, whereas only dexamethasone decreased FEglutamine in glutamine loaded rats. Therefore it can be concluded that the hormonal control of renal amino acid handling is not unique. The following reasons might be responsible for the hormonal stimulation of renal amino acid reabsorption (cp. FLECK et al. 1997): Dexamethasone induces the gene expression and might enhance the content of carrier molecules in the tubular cells (YAMAMOTO 1985). Also T3 is reported to increase the synthesis of proteins in the kidney (CAPASSO et al. 1987). Dexamethasone (BAUM and QUIGLEY 1993) and T3 (GUERNSEY and EDELMANN 1984) enhance the activity of the Na+/K+-ATPase and increase the sodium gradient between tubular lumen and tubular cell. This might increase the highly sodium dependent amino acid reabsorption (Y AO et al. 1994). The potassium permeability at the basolateral membrane of the tubular cells is increased after T3 administration (DE NA YER 1987) and might cause an enhanced Na+/K+-ATPase activity, too. GORDON et al. (1986) found an increased calcium uptake in heart cells after T3 treatment. If it also occurs in the kidney, it might activate adenylate cyclase activity via calmodulin, increase the cAMP content and enhance amino acid transport capacity. The taurine uptake in cell cultures appears to be regulated by thyrotropin through cAMP (JHIANG et al. 1993). Perhaps there is an influence ofT3, too. The reason for the lack of effect of T3 in glutamine loaded and of dexamethasone in taurine loaded rats remains to be clarified. Possibly the metabolic actions of the two hormones could mask their renal effects. Taurine is one of the end products of sulfur metabolism (HUXTABLE 1992). Therefore it is not necessary to increase its reabsorption at all. On the other hand, because of enhanced metabolism within the renal tubular cells after hormone treatment, the so-called house-keeping of the tubular cells 438

Exp Toxic Pathol50 (1998) 4-6

requires higher amounts of amino acids followed by a nonspecific increase in the cellular uptake of amino acids from the blood (FOULKES and BLANCK 1990). This uptake is followed by an enhanced intracellular amino acid concentration and, therefore, by a reduced concentration gradient between tubular fluid and tubular cell. This might be the reason for a diminished driving force for amino acid reabsorption and might mask stimulatory hormone effects at the luminal site. Nevertheless, the reason for different effects of T3 and dexamethasone on renal amino acid handling should be clarified in further experiments at the cellular level.

References BAUM M, QUIGLEY R: Glucocorticoids stimulate rabbit proximal convoluted tubule acidification. J Clin Invest 1993; 91: 110-114 BRAuNLICH, H: Postnatal development of kidney function in rats receiving thyroid hormones. Exp Clin Endokrinol 1984; 83: 243-250 BRAuNLICH, H, KOHLER A, SCHMIDT I: Acceleration of paminohippurate excretion in immature rats by dexamethasone treatment. Med Bioi 1986; 64: 267-270 BREZIS M, SILVA P, EpSTEIN FH: Amino acid induced renal vasodilatation in isolated perfused kidney: coupling to oxidative metabolism. Am 1 Physiol1984; 247: H999-H1 004 CAPASSO 0, DE SANTO NO, KINNE R: Thyroid hormones and renal transport: Cellular and biochemical aspects. Kidney Int 1987; 32: 443-451 CHESNEY RW, BUDREAU AM: Inhibitors of anion exchanger activity reduce sodium chloride-dependent taurine transport by brush border vesicles. Adv Exp Med Bioi 1994; 359: 111-120 CHESNEY RW, OUSOWSKI N, DABBAGH S, et al.: Factors affecting the transport of ~-amino acids in rat renal brush border membrane vesicles. Biochim Biophys Acta 1985; 812: 702-712 CHESNEY RW, ZELIKOVIC I, FRIEDMAN AL, et al.: Renal taurine transport - recent developments. Adv Exp Med BioI 1987; 217: 49-59 COLLARINI E1, OXENDER DL: Mechanisms of transport of amino acids across membranes. Ann Rev Nutr 1987; 7: 75-90 DE NA YER P: Thyroid hormone action at the cellular level. Hormone Res 1987; 26: 48-57 FLECK C: Renal transport of endogenous amino acids. I. Comparison between immature and adult rats. Renal Physiol Biochem 1992; 15: 257-265 FLECK C, AURICH M, SCHWERTFEGER M: Stimulation of renal amino acid reabsorption after treatment with triiodothyronine or dexamethasone in amino acid loaded rats. Amino Acids 1997; 12,265-279 FLECK C, PERTSCH 1: Epidermal growth factor (EOF) increases the renal amino acid transport capacity in amino acid loaded rats. Amino Acids 1998 (in press) FOULKES EC, BLANCK S: Site of uptake of non filtered amino acid in rabbit kidney. Proc Soc Exp BioI Med 1990; 193: 56-60 FRIEDMAN AL, ALBRIGHT PW, OUSOWSKI N, et al.: Renal adaptation to alteration in dietary amino acid intake. Am 1 Physioll983; 245: F159-F166

GORDON A, SCHWARTZ H, GROSS 1: The stimulation of sugar transport in heart cells grown in a serum-free medium by picomolar concentrations of thyroid hormones: the effect of insulin and hydrocortisone. Endocrinol 1986; 18: 52-57 GUERNSEY DL, EDELMAN IS: Regulation of thermogenesis by thyroid hormones. In: Molecular basis of thyroid hormone action. Eds.: Oppenheimer JH, Samuels HH, Academic Press, New York, 1983; pp 293-324 GUTMANN M, HorSCHEN C, KRAMER R: Carrier mediated glutamate secretion by corynebacterium glutamicum under biotin limitation. Biochim Biophys Acta 1993; 1112: 115-123 HUXTABLE RJ: Physiological action of taurine. Physiol Rev 1992; 72: 101-163 JEAN T, POUJEOL P, RIPOCHE P: Taurine transport in brush border membrane vesicles isolated from hyper- and normotaurinuric mouse kidney. Ren Physio1 1984; 7: 349-356 JESSEN H: Taurine and ~-a1anine transport in an established human kidney cell line derived from the proximal tubule. Biochim Biophys Acta 1994; 1194: 44-52 JESSEN H, RorGAARD H, JACOBSEN C: Uptake of neutral alpha- and beta-amino acids by human proximal tubular cells. Biochim Biophys Acta 1996; 1282: 225-232 JHIANG SM, FITHIAN L, SMANIK P, et al.: Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett 1993; 318: 139-144 KING PA, BEYENBACH KW, GOLDSTEIN L: Taurine transport by isolated flounder renal tubules. J Exp Zool1982; 223: 103-114 KOENIG H, GOLDSTONE A, Lu CY: Testosterone induced a rapid stimulation of endocytosis, amino acid and hexose transport in mouse kidney cortex. Biochem Biophys Res Commun 1982; 106: 346-353 LIU QR, LOPEZ-CORCUERA B, NELSON H, et al.: Cloning and expression of a cDNA encoding the transporter of taurine and ~-alanine in mouse brain. Proc Natl Acad Sci U.S.A. 1992; 89: 12145-12149 RAMAMOORTHY S, LEIBACH FH, MAHESH VB, et al.: Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem J 1994; 300: 893-900

ROTH, M, HAMPAI A: Column chromatography of amino acids with fluorescence detection. J. Chromatogr. 1973; 83: 353-356 SCRIVER CR, BERGERON M: Amino acid transport in kidney. The use of mutation to dissect membrane and transepithelial transport. In: Heritable disorders of amino acid metabolism, Ed.: W. L. Nyhan. Willey, New York, 1974; pp.515-592 SILBERNAGL S: Kinetics and localization of tubular resorption of "acidic" amino acids. A microperfusion and free flow micropuncture study in rat kidney. Pfliigers Arch Eur J Physio1 1983; 396: 218-224 SILBERNAGL S: The renal handling of amino acids and oligopeptides. Physiol Rev 1988; 68: 911-1007 SILBERNAGL S, VOLKER K, LANG H-J, DANZLER WE: Taurine reabsorption by a carrier interacting with furosemide in short and long Henle's loops of rat nephron. Am J Physio11997; 272: F205-F213 SOHTELL M, KALMARK B, ULFENDAHL H: FITC-inulin as a kidney tubule marker in the rat. Acta Physiol Scand 1983; 119: 313-316 TIETZE IN, SORENSEN S, ErSKJAER H, et al.: Tubular handling of amino acids after intravenous infusion of amino acids in healthy humans. Nephrol Dial Transplant 1992; 7: 493-500 UCHIDA S, KWON HM, YAMAUCHI A, et al.: Molecular cloning of the cDNA for an MDCK cell Na+- and Cl--dependent taurine transporter that is regulated by hypertonicity. Proc Natl Acad Sci U.S.A. 1992; 89: 8230-8234 YAMAMOTO K: Steroid receptor regulated transcription of specific genes and gene networks. Ann Rev Genet 1985; 19: 209-252 YAO SY, MAZYKA WR, ELLIOT JF, et al.: Poly (AY RNA from the mucosa of rat jejunum induces novel Na+-dependent and Na+ -independent leucine transport activities in oocytes of Xenopus laevis. Molec Membrane Biol1994; 11: 109-118 ZELIKovrc I, CHESNEY RW: Sodium-coupled amino acid transport in renal tubule. Kidney Int 1989; 9: 49-55

Exp Toxic Pathol50 (1998) 4-6

439