TAURINE MODULATION OF RENAL EXCRETORY FUNCTION

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THAI JOURNAL OF PHYSIOLOGICAL SCIENCES

Volume 16 (No.3, December 2003)

Page 83 - 90

www.tjps.org

ISSN 0857 - 5754

Review Article

TAURINE MODULATION OF RENAL EXCRETORY

FUNCTION

Mahmood S. Mozaffari

Department of Oral Biology and Maxillofacial Pathology, Medical College of Georgia School

of Dentistry, Augusta, Georgia 30912-1128

Taurine is an important regulator of cellular ion transport and osmotic balance, aspects that are pivotal

to renal function. The kidney not only regulates body taurine status, but emerging information also

suggests that body taurine status is of consequence for renal function. While reduction in endogenous

taurine stores can attenuate renal excretory function, exogenous taurine supplementation is

renoprotective and augments kidney function in several conditions that are associated with reduction in

diuresis and natriuresis. Thus taurine treatment may be of potential benefit in conditions that are

associated with impaired kidney function and the accompanying dysregulation of body fluid and

electrolyte homeostasis.

Key words:

taurine, kidney function

taurine (2-aminoethanesulfonic acid) is an amino acid found in high concentration in mammalian cells.

A number of physiological roles have been attributed to taurine including bile acid conjugation,

neurotransmission/ neuromodulation, retinal cell stabilization, antioxidation, and regulation of ion

transport and osmotic balance, with the regulation of ion transport being particularly important (Burg,

1995; Fugelli et al., 1995; Handler and Kwon, 1993; Huxtable, 1992; Pasantes-Morales and Martin,

1990; Pasantes-Morales et al., 1998; Schaffer et al., 2000; Uchida et al., 1991). The evidence in

support of a role for taurine in the regulation of ion transport include: a) the demonstration that taurine

transport per se is directly coupled to sodium and chloride flux, a process involving the transport of

taurine with a stoichiometry of 2-3 Na

; 1Cl

; 1 taurine (Benyajati and Bay, 1994; Zelikovic et al.,

1989) and b) during periods of osmotic stress, the cell modulates the levels of organic osmolytes, such

as taurine, and inorganic osmolytes, such as sodium, in order to re-establish osmotic homeostasis

(Fugelli et al., 1995; Handler and Kwon, 1993; Schaffer et al., 2000; Uchida et al., 1991). Clearly the

effects of taurine on cellular ion transport and osmotic balance are of major relevance to kidney

function. Thus, given the pivotal role of the kidney in regulation of body fluid and electrolyte balance,

this review will focus on the role of endogenous taurine stores as well as exogenous taurine

supplementation on kidney function.

Role of endogenous taurine in regulation of

kidney function

There is a heterogeneous distribution of

taurine in the kidney with intracellular taurine con-

centration increasing along the corticomedullary

Received: October 21, 2003 ; accepted: November 3, 2003

Correspondence should be addressed to Dr. Mahmood

S. Mozaffari, Department of Oral Biology and

Maxillofacial Pathology; CB 3710, Medical College of

Georgia Augusta, Georgia 30912-1128

Phone: (706) 721-3181, FAX: (706) 721-6276,

E-mail: Mmozaffa@mail.mcg.edu

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Mozaffari MS

axis (Amiry-Moghaddam et al., 1994). As a result, there in preferential localization of taurine to the

inner medullary regions of the kidney, where the extracellular milieu can become extremely

hypertonic. The differential taurine distribution is believed to serve as an adaptive mechanism for renal

tubular cells to cope with high osmotic gradient of the medullary interstitium (Nakanishi et al., 1994).

Recent studies suggest that taurine depletion is of consequence for kidney function. This

information has been gleaned from studies with the drug-induced taurine-deficient rat. Reduction of

tissue taurine content can be achieved by providing taurine uptake inhibitors such as β-alanine or

guanidinoethylsulphonate (GES) in drinking solution (Lombardini, 1996; Mozaffari et al., 1986;

Shaffer and Kocsis, 1981). While GES can be more effective in reducing tissue taurine content, it also

accumulates in the tissue (Mozaffari et al., 1986). By contrast, β-alanine does not accumulate in the

cell as it is readily metabolized to

malonic semialdehyde and eliminated as carbon dioxide (Shaffer and

Kocsis, 1981)

. Thus in order to avoid the potential confounding influence of accumulation of the taurine

depleting agent in the tissue, we have used the β-alanine-induced taurine deficient rat to examine the

impact of endogenous tissue taurine store on kidney function (Mozaffari et al., 1997; Mozaffari et al.,

1998). Rats given 3% β-alanine in their drinking fluid for three weeks display a significant reduction

(~ 40%) in taurine content of tissues such as the kidney, the heart and the submandibular gland

(Lombardini, 1996; Mozaffari et al., 1986; Shaffer and Kocsis, 1981).

Utilizing the taurine-deficient rat, our initial studies focused on the ability of the animal to

dispose of a saline volume load (Mozaffari et al., 1997). We found that while the initial rates of fluid

and sodium excretion in response to intravenous administration of an isotonic saline load (equivalent to

5% of the animal’s body weight) were reduced in the taurine deficient rat, the overall ability of the

kidney to dispose of the volume challenge, over 90 minutes, was minimally affected (Mozaffari et al.,

1997).

We next explored the possibility that while taurine deficiency does not affect the ability of the

animal to dispose of an isotonic saline load, it may be of consequence for excretion of hypotonic and/or

hypertonic saline solution (Mozaffari et al., 1998). This contention was based on several lines of

evidence. First, there is a growing body of evidence firmly establishing a major role for taurine in

cellular adaptation to osmotic stress. Exposure of a variety of cells to a hypotonic solution results in

cellular extrusion of taurine, a process which contributes to regulatory volume decrease. Conversely,

exposure of cells to hypertonic media results in cellular uptake of taurine, an important mechanism in

regulatory volume increase (Burg, 1995; Fugelli et al., 1995; Handler and Kwon, 1993; Pasantes-

Morales and Martin, 1990; Pasantes-Morales et al., 1998; Schaffer et al., 2000; Uchida et al., 1991).

Second, renal tubular cells normally experience large changes in tonicity. The intracellular

accumulation of organic osmolytes, i.e., taurine, by renal tubular cells serves as an adaptive mechanism

to cope with an increase in interstitial osmolality; the high interstitial osmolality is established by the

counter current multiplier system and is essential for the kidney to concentrate urine. Therefore, we

expected taurine to contribute to the counter current mechanism of urinary concentration, a deficiency

of which would affect renal excretory function. Third, taurine is invariably linked to regulatory volume

changes because of its role as an osmolyte (Fugelli et al., 1995; Handler and Kwon, 1993; Pasantes-

Morales and Martin, 1990; Pasantes-Morales et al., 1998; Schaffer et al., 2000; Uchida et al., 1991).

Since major changes in taurine flux occur in response to altered osmotic conditions, we also expected

taurine movement to influence fluid and sodium excretion by the kidney. Against this background, we

determined whether a reduction in endogenous taurine stores would differentially affect renal excretory

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taurine and the renal

responses to an intravenous infusion of a hypertonic vs. a hypotonic saline solution (Mozaffari et al.,

1998).

The results indicated that while taurine deficiency was associated with a reduction in the ability

of the animal to dispose of a hypotonic saline load, the excretion of a hypertonic saline challenge was

not affected despite the requirement to eliminate more sodium (Mozaffari et al., 1998). Taken together,

the data suggested that it is unlikely that taurine deficiency adversely affects the ability of the kidney to

concentrate urine. This may relate to the fact that β-alanine treatment reduces renal taurine content by

~ 40% and that greater reductions may be required to impair the urinary concentrating ability. In

subsequent studies, we explored the basis for the differential responses of the taurine deficient rat to

hypotonic saline solution by examining potential involvement of arginine vasopressin (AVP) system

(Mozaffari and Schaffer, 2001).

Based on our observation of differential renal excretory responses of the taurine deficient rat to

hypotonic and hypertonic saline solutions and those of other investigators regarding taurine-modulation

of AVP secretion (Deleuze et al., 1998; Hussy et al., 1997; Miyata et al., 1997), we conjectured that the

inhibitory influence of taurine in regulation of AVP secretion would be attenuated in rats deficient of

taurine, resulting in an overactive AVP system. Therefore, we tested the hypothesis that taurine-

depleted rats manifest increased plasma AVP concentration thereby causing augmented AVP-mediated

renal responses, and determined whether these effects are reversed by taurine repletion. As a corollary,

we also tested whether taurine supplementation attenuates AVP-mediated renal responses.

Accordingly, renal effects of a peptide antagonist for the renal V

receptors were determined in the

conscious control, taurine-depleted, taurine-repleted and taurine-supplemented rats along with

determination of plasma AVP concentration (Mozaffari and Schaffer, 2001).

We found that control and taurine-supplemented rats displayed similar and significant AVP

receptor antagonist-induced elevations in fluid excretion, sodium excretion and free water clearance but

a marked reduction in urine osmolality; analysis of the data suggested that the effect of the antagonist

on renal excretory function is related, primarily, to altered tubular reabsorption activity. These effects

were consistent with inhibition of endogenous AVP activity. By contrast, in the taurine-depleted rats,

the magnitude and the time course of drug-induced renal excretory responses lagged behind those of

the control and taurine-supplemented groups. Further, baseline urine osmolality was significantly

higher in the taurine-depleted compared to the control or taurine-supplemented groups. However,

following administration of the antagonist, taurine-depleted rats manifested a delayed but more marked

reduction in urine osmolality thereby eliminating the baseline differential that existed between the

taurine-depleted rats and control or taurine-supplemented groups. Consistent with these observations,

plasma AVP was significantly increased in the taurine-depleted compared to the control rats.

Interestingly, taurine-repletion shifted all responses closer to the control group. These observations

suggested that taurine modulates renal function, and thereby body fluid homeostasis, through an AVP-

dependent mechanism. Although the impact of taurine on cellular adaptation to osmotic stress has been

the focus of numerous investigations, our study was the first to also implicate a prominent role for

endogenous taurine in regulation of body fluid homeostasis.

Effects of exogenous taurine supplementation on kidney function

While the impact of endogenous taurine stores on kidney function has received little attention,

the impact of exogenous taurine supplementation on renal, and cardiovascular, function has been the

focus of numerous reports (Chiba et al., 2002; Cruz et al., 2000; Dawson, Jr. et al., 2000; Dlouha and

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Mozaffari MS

McBroom, 1986; Erdem et al., 2000; Gentile et al., 1994; Ideishi et al., 1994; Kohashi et al., 1989;

Militante and Lombardini, 2002; Mozaffari et al., 2003; Schaffer et al., 2003; Trachtman et al., 1993;

Trachtman et al., 1995). These studies have addressed the effect of taurine therapy on blood pressure

as well as in retarding/preventing renal abnormalities in disease states and aging. An antihypertensive

effect of exogenous taurine therapy has been reported in most, but not all (Dawson, Jr. et al., 2000;

Mozaffari et al., 2003), animal models of systemic hypertension as were recently reviewed by

Milatante and Lombardini (Militante and Lombardini, 2002). Thus the following discussion will

primarily focus on the effect of taurine on kidney function.

taurine reportedly possesses antioxidant and membrane-stabilizing properties (Schaffer et al.,

2003). Several studies have proposed that taurine is renoprotective by virtue of its antioxidative

activity. In one such study, Trachtman and colleagues reported that rats supplemented with taurine

became resistant to kidney damage and proteinuria caused by either aminonucleoside-induced

glomerulopathy or streptozotocin-induced type 1 diabetes (Trachtman et al., 1993). In a related study,

chronic taurine treatment prevented aging-related upregulation of TGF-β1, collagen types I and IV and

fibronectin mRNAs, proteins involved in the development of renal fibrosis in aging rat (Cruz et al.,

2000). The renoprotective effect of exogenous taurine therapy has also been confirmed utilizing

several animal models of hypertension including the Dahl salt-sensitive rat (Chiba et al., 2002;

Militante and Lombardini, 2002). While the antihypertensive effect of taurine supplementation has

been attributed, in part, to suppression of the sympathetic nervous system activity and augmented

natriuresis (Inoue et al., 1988), few studies have provided direct evidence for the impact of exogenous

taurine on excretory function.

We initially examined the effect of acute taurine treatment on the ability of the conscious rat to

dispose of an isotonic saline load (Mozaffari et al., 1997). We found that inclusion of taurine in the

infusate increased the diuretic and natriuretic responses to a saline load and these effects were more

prominent in animals maintained on a basal, compared to a high NaCl diet. These observations

corroborated the findings of Gentile and colleagues (1994) who had reported that taurine causes

significant improvement in renal excretory responses in cirrhotic patients with ascites.

Based on the reported renoprotective effect of chronic taurine treatment as well the effect of

acute taurine supplementation on renal excretory responses to a saline challenge, we sought to

determine whether long-term taurine therapy would benefit renal excretory capacity of a compromised

kidney. We had previously shown that surgical removal of one kidney early in life, results in

progressive decline in the ability of the remaining kidney to dispose of a saline volume challenge as the

animal aged (Mozaffari and Wyss, 1999; Mozaffari and Schaffer, 2002); this effect was evident

earlier in animals that were injected with streptozotocin as a neonate at 2 days of age (Mozaffari and

Schaffer, 2002a). It is noteworthy that injection of streptozotocin into an adult rat results in destruction

of pancreatic β cells and a syndrome similar to type 1 diabetes (Schaffer and Mozaffari, 1999). By

contrast, neonatal streptozotocin-treated rats develop a state of impaired glucose tolerance as they reach

adulthood, in part, due to the ability of neonate rat to partially regenerate β cell mass (Schaffer and

Mozaffari, 1999). Since impaired glucose tolerance is the “lead in” phase to overt type 2 diabetes

(Mozaffari and Schaffer, 2002), the neonatal stretptozotocin-treated rat is a logical animal model to

explore the impact of glucose intolerance on target organs.

We found that chronic taurine treatment ameliorated the reduction in saline-induced diuresis

and natriuresis by both the unilaterally nephrectomized (UNX) control and the UNX glucose intolerant

rat (Mozaffari and Schaffer, 2002). Both an increase in glomerular filtration and a reduction in

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taurine and the renal

tubular reabsorption of fluid and sodium caused this taurine-mediated improvement in renal excretory

function. Interestingly, taurine supplementation also caused reduction in proteinuria in both the UNX

control and UNX glucose intolerant rats further indicating renoprotection (Mozaffari and Schaffer,

2002).

A noted feature of the UNX control and UNX glucose intolerant rat is that blood pressure

remains within the normal range as the animal ages; taurine treatment did not affect blood pressure in

these rats (Mozaffari and Schaffer, 2002). Given earlier reports of its antihypertensive effect as well as

the beneficial effect of long-term taurine treatment in retarding the age-related reduction in renal

excretory function of the UNX rat (Militante and Lombardini, 2002; Mozaffari and Schaffer, 2002), we

next examined the potential benefits of taurine supplementation on renal excretory function and blood

pressure of the hypertensive and hypertensive-glucose intolerant rats (Mozaffari et al., 2003). The

hypertensive animal models were produced in our laboratory by feeding the UNX control and UNX

glucose-intolerant rats a diet which contains a high (8%) NaCl content (hypertensive and hypertensive-

glucose intolerant rat, respectively) (Mozaffari et al., 2000; Mozaffari and Schaffer, 2002; Mozaffari et

al., 2003). The vehicle-treated hypertensive-glucose intolerant rats displayed reduced saline volume-

induced diuresis and natriuresis relative to their hypertensive counterparts. While taurine treatment did

not affect blood pressure in either group, it did increase renal excretory responses to saline volume

loading in the hypertensive glucose intolerant, but not the hypertensive control, group (Mozaffari et al.,

2003). As a result, the differential which existed between the vehicle-treated hypertensive and

hypertensive-glucose intolerant groups was eliminated by chronic taurine treatment. The effect of

taurine on renal excretory function of the hypertensive glucose-intolerant rats primarily related to

reduced tubular reabsorption activity (Mozaffari et al., 2003). The lack of an effect of taurine on blood

pressure despite augmentation of renal excretory function is suggestive of a beneficial resetting of the

pressure-diuresis-natriuresis mechanism in the hypertensive glucose-intolerant rat. In addition, taurine

treatment reduced protein excretion further confirming its renoprotective effect.

Perspective

Our studies to date indicate that endogenous taurine stores are of consequence for regulation of

renal excretory function. Nonetheless, the contribution of regulatory mechanisms, other than AVP, to

the effect of taurine deficiency on kidney function has not been explored. Of potential relevance are

angiotensin II and the atrial natriuretic peptide which are considered as physiological antagonists with

respect to regulation of renal and cardiovascular functions. There is growing evidence that taurine

opposes some of the actions of actions of taurine (Schaffer et al., 2000). In addition, atrial extracts of

taurine-treated cardiomyopathic hamsters increases renal fluid and sodium excretion (Dlouha and

McBroom, 1986). Thus the depressant effect of taurine depletion on renal excretory function may

relate to modulation of mechanisms involved in regulation of glomerular function and tubular

reabsorption activity. This contention is supported by our observation that exogenous taurine

supplementation ameliorates the deficiency in diuresis and natriuresis by enhancing glomerular

function and/or reducing tubular reabsorption activity. Thus investigation of the mechanisms by which

taurine affects kidney function is of relevance to several disorders that are associated with

dysregulation of body fluid and electrolyte balance (i.e., systemic hypertension, heart failure and

diabetes mellitus).

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Mozaffari MS

Acknowledgement

This study was supported by Taisho Pharmaceutical Company, Ltd.

References

1. Amiry-Moghaddam M, Nagelhus E, and Ottersen OP. Light- and electronmicroscopic distribution of

taurine, an organic osmolyte, in rat renal tubule cells. Kidney Int 45: 10-22, 1994.

2. Benyajati S and Bay SM. Basolateral taurine transport system in reptilian renal cells. Am J Physiol

266: F439-F449, 1994.

3. Burg MB. Molecular basis of osmotic regulation. Am J Physiol 268: F983-F996, 1995.

4. Chiba Y, Ando K, and Fujita T. The protective effects of taurine against renal damage by salt

loading in Dahl salt-sensitive rats. J Hypertens 20: 2269-2274, 2002.

5. Cruz CI, Ruiz-Torres P, del Moral RG, Rodriguez-Puyol M, and Rodriguez-Puyol D. Age-related

progressive renal fibrosis in rats and its prevention with ACE inhibitors and taurine. Am J Physiol

Renal Physiol 278: F122-F129, 2000.

6. Dawson R, Jr., Liu S, Jung B, Messina S, and Eppler B. Effects of high salt diets and taurine on the

development of hypertension in the stroke-prone spontaneously hypertensive rat. Amino Acids 19: 643-

665, 2000.

7. Deleuze C, Duvoid A, and Hussy N. Properties and glial origin of osmotic-dependent release of

taurine from the rat supraoptic nucleus. J Physiol 507 ( Pt 2): 463-471, 1998.

8. Dlouha H and McBroom MJ. Atrial natriuretic factor in taurine-treated normal and cardiomyopathic

hamsters. Proc Soc Exp Biol Med 181: 411-415, 1986.

9. Erdem A, Gundogan NU, Usubutun A, Kilinc K, Erdem SR, Kara A, and Bozkurt A. The protective

effect of taurine against gentamicin-induced acute tubular necrosis in rats. Nephrol Dial Transplant 15:

1175-1182, 2000.

10. Fugelli K, Kanli H, and Terreros DA. taurine efflux is a cell volume regulatory process in

proximal renal tubules from the teleost Carassius auratus. Acta Physiol Scand 155: 223-232, 1995.

11. Gentile S, Bologna E, Terracina D, and Angelico M. taurine-induced diuresis and natriuresis in

cirrhotic patients with ascites. Life Sci 54: 1585-1593, 1994.

12. Handler JS and Kwon HM. Regulation of renal cell organic osmolyte transport by tonicity. Am J

Physiol 265: C1449-C1455, 1993.

13. Hussy N, Deleuze C, Pantaloni A, Desarmenien MG, and Moos F. Agonist action of taurine on

glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation. J Physiol

502 ( Pt 3): 609-621, 1997.

14. Huxtable RJ. Physiological actions of taurine. Physiol Rev 72: 101-163, 1992.

15. Ideishi M, Miura S, Sakai T, Sasaguri M, Misumi Y, and Arakawa K. taurine amplifies renal

kallikrein and prevents salt-induced hypertension in Dahl rats. J Hypertens 12: 653-661, 1994.

16. Inoue A, Takahashi H, Lee LC, Sasaki S, Kohno Y, Takeda K, Yoshimura M, and Nakagawa M.

Retardation of the development of hypertension in DOCA salt rats by taurine supplement. Cardiovasc

Res 22: 351-358, 1988.

17. Kohashi N, Okabayashi T, Horiuchi M, Nishiyama H, Takenaka T, and Katori R. Mechanism of

taurine natriuresis in rats. Adv Exp Med Biol 247A: 635-640, 1989.

18. Lombardini JB. taurine depletion in the intact animal stimulates in vitro phosphorylation of an

approximately 44-kDa protein present in the mitochondrial fraction of the rat heart. J Mol Cell Cardiol

28: 1957-1961, 1996.

Page 7

taurine and the renal

19. Militante JD and Lombardini JB. Treatment of hypertension with oral taurine: experimental and

clinical studies. Amino Acids 23: 381-393, 2002.

20. Miyata S, Matsushima O, and Hatton GI. taurine in rat posterior pituitary: localization in

astrocytes and selective release by hypoosmotic stimulation. J Comp Neurol 381: 513-523, 1997.

21. Mozaffari MS, Azuma J, Patel C, and Schaffer SW. Renal excretory responses to saline load in the

taurine-depleted and the taurine-supplemented rat. Biochem Pharmacol 54: 619-624, 1997.

22. Mozaffari MS, Miyata N, and Schaffer SW. Effects of taurine and enalapril on kidney function of

the hypertensive glucose-intolerant rat. Am J Hypertens 16: 673-680, 2003.

23. Mozaffari MS, Patel C, Warren BK, and Schaffer SW. NaCl-induced hypertensive rat model of

non-insulin-dependent diabetes: role of sympathetic modulation. Am J Hypertens 13: 540-546, 2000.

24. Mozaffari MS and Schaffer D. taurine modulates arginine vasopressin-mediated regulation of renal

function. J Cardiovasc Pharmacol 37: 742-750, 2001.

25. Mozaffari MS and Schaffer SW. Chronic taurine treatment ameliorates reduction in saline-induced

diuresis and natriuresis. Kidney Int 61: 1750-1759, 2002.

26. Mozaffari MS and Schaffer SW. Impaired saline-stimulated diuresis and natriuresis in the

conscious hypertensive glucose-intolerant rat. Am J Hypertens 15: 58-65, 2002.

27. Mozaffari MS, Tan BH, Lucia MA, and Schaffer SW. Effect of drug-induced taurine depletion on

cardiac contractility and metabolism. Biochem Pharmacol 35: 985-989, 1986.

28. Mozaffari MS, Warren BK, Azuma J, and Schaffer SW. Renal excretory responses of taurine-

depleted rats to hypotonic and hypertonic saline infusion. Amino Acids 15: 109-116, 1998.

29. Mozaffari MS and Wyss JM. Dietary NaCl-induced hypertension in uninephrectomized Wistar-

Kyoto rats: role of kidney function. J Cardiovasc Pharmacol 33: 814-821, 1999.

30. Nakanishi T, Takamitsu Y, and Sugita M. Role of taurine in the kidney: osmoregulatory taurine

accumulation in renal medulla. Adv Exp Med Biol 359: 139-148, 1994.

31. Pasantes-Morales H and Martin DR. taurine and mechanisms of cell volume regulation. Prog Clin

Biol Res 351: 317-328, 1990.

32. Pasantes-Morales H, Quesada O, and Moran J. taurine: an osmolyte in mammalian tissues. Adv

Exp Med Biol 442: 209-217, 1998.

33. Schaffer S, Takahashi K, and Azuma J. Role of osmoregulation in the actions of taurine. Amino

Acids 19: 527-546, 2000.

34. Schaffer SW, Azuma J, Takahashi K, and Mozaffari MS. Why is taurine cytoprotective? Adv Exp

Med Biol 526: 307-322, 2003.

35. Schaffer SW, Lombardini JB, and Azuma J. Interaction between the actions of taurine and

angiotensin II. Amino Acids 18: 305-318, 2000.

36. Schaffer SW and Mozaffari MS. The neonatal STZ model of diabetes. In: Experimental Models of

Diabetes, edited by Messina S. Boca Raton: CRC Press LLC, 1999, p. 231-255.

37. Shaffer JE and Kocsis JJ. taurine mobilizing effects of beta alanine and other inhibitors of taurine

transport. Life Sci 28: 2727-2736, 1981.

38. Trachtman H, Futterweit S, Maesaka J, Ma C, Valderrama E, Fuchs A, Tarectecan AA, Rao PS,

Sturman JA, and Boles TH. taurine ameliorates chronic streptozocin-induced diabetic nephropathy in

rats. Am J Physiol 269: F429-F438, 1995.

39. Trachtman H, Lu P, and Sturman JA. Immunohistochemical localization of taurine in rat renal

tissue: studies in experimental disease states. J Histochem Cytochem 41: 1209-1216, 1993.

Page 8

Mozaffari MS

40. Uchida S, Nakanishi T, Kwon HM, Preston AS, and Handler JS. taurine behaves as an osmolyte in

Madin-Darby canine kidney cells. Protection by polarized, regulated transport of taurine. J Clin Invest

88: 656-662, 1991.

41. Zelikovic I, Stejskal-Lorenz E, Lohstroh P, Budreau A, and Chesney RW. Anion dependence of

taurine transport by rat renal brush-border membrane vesicles. Am J Physiol 256: F646-F655, 1989.