Taurine, a sulfonic acid analog of beta-alanine and an important osmoregulator in mammals, undergoes a renal adaptive response to altered dietary intake of sulfur amino acids. Dietary taurine (LTD) restriction induces a higher initial rate Vmax of NaCl-induced taurine symport in rat renal brush border membrane vesicles (BBMV) and enhanced reabsorption of filtered taurine as compared to rats fed a normal taurine diet (NTD). A high taurine diet (HTD) enhances urinary taurine excretion and induces a decline in the Vmax of the same symporter. Taurine is translocated by means of a 2Na:l Cl:l taurine quaternary complex 'carrier' and an inside negative potential, but the precise details of transport are unclear, as are the mechanisms signaling the adaptive response. Evidence in BBMV and continuous cultured renal cell lines (LLC-PK1 and MDCK) suggest that the adaptive response may be triggered by changes in renal intracellular taurine content and that increased or reduced import of carrier relates to cell membrane trafficking or import by the microtrabecular network, because transporter import into membranes is blocked by colchicine. New protein synthesis is also important since cycloheximide blocks the adaptive response. The mechanisms responsible for the adaptive response and maintenance of taurine homeostasis will be further examined both in continuous renal cell culture and in BBMV by exploring the following hypotheses: ( 1 ) The signal for the renal adaptive response relates to intracellular rather than extracellular taurine content. ( 2 ) The renal adaptive response demonstrates an asymmetric polarity with enhanced (or reduced) uptake across the apical membrane and enhanced (or reduced) efflux across the basolateral surface. ( 3 ) A rapid adaptive response represents changes in cellular trafficking or """"""""shuttling"""""""" of the taurine symporter, but the prolonged (8-14 day) response requires new protein synthesis. ( 4 ) The renal adaptive response as well as taurine symport activity requires first chloride and then sodium or taurine interaction with the carrier prior to translocation across the apical membrane. ( 5 ) The renal adaptive response may serve to enhance both taurine and chloride uptake by renal epithelium. ( 6 ) The prolonged adaptive response involves transcription of increased amounts of messenger RNA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK037223-08
Application #
2140014
Study Section
General Medicine B Study Section (GMB)
Project Start
1988-05-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1995-03-31
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Chesney, R W; Helms, R A; Christensen, M et al. (1998) The role of taurine in infant nutrition. Adv Exp Med Biol 442:463-76
Chesney, R W; Helms, R A; Christensen, M et al. (1998) An updated view of the value of taurine in infant nutrition. Adv Pediatr 45:179-200
Matsell, D G; Bennett, T; Han, X et al. (1997) Regulation of the taurine transporter gene in the S3 segment of the proximal tubule. Kidney Int 52:748-54
Koo, W W; Chesney, R W; Mitchell, N (1995) Case report: effect of pregnancy on idiopathic juvenile osteoporosis. Am J Med Sci 309:223-5
Jones, D P; Jiang, B; Chesney, R W (1994) Regulation of taurine transport by external taurine concentration and medium osmolality in renal tubular cells in culture. Adv Exp Med Biol 359:131-8
Panchenko, E L; Chesney, R W; Roy 3rd, S et al. (1994) The differential diagnostic value of urinary enzyme and amino acid excretion in children with nephrotic syndrome. Pediatr Nephrol 8:142-7
Chesney, R W; Jones, D; Zelikovic, I (1993) Renal amino acid transport: cellular and molecular events from clearance studies to frog eggs. Pediatr Nephrol 7:574-84
Chesney, R W; Budreau, A M (1993) Efflux of taurine from renal brush border membrane vesicles: is it adaptively regulated? Pediatr Nephrol 7:35-40
Jones, D P; Miller, L A; Chesney, R W (1993) Polarity of taurine transport in cultured renal epithelial cell lines: LLC-PK1 and MDCK. Am J Physiol 265:F137-45
Jones, D P; Chesney, R W (1992) Development of tubular function. Clin Perinatol 19:33-57

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