The B-amino acid, taurine, is a stabilizer of neural membranes and an osmoregulator whose body homeostasis is maintained by the kidney. Rats fed a low taurine diet have a 90% fall in urine taurine excretion and an increase in the initial rate of Na+-taurine symport into brush border membrane vesicles (BBMV) - the renal adaptive response to altered sulfur amino acid uptake. High dietary taurine results in taurinuria and a fall in initial rate Vmax into BBMV. Factors causing a fall in renal cortex taurine content enhance Na+-taurine symport and serve as a signal for the adaptive response. Taurine uptake into BBMV not only depends on an external Na+-gradient but external Cl- appears to be a preferred anion to support Na+-taurine symport. Since the adaptive response is a membrane-related event, this proposal will explore a series of hypotheses concerning the relationship between the renal adaptive response and Na+-taurine symport activity. 1. Factors which increase conducted Na+-uptake in animals on an ordinary diet, i.e. valinomycin and nigericin will enhance the adaptive increase in taurine uptake and increase uptake in HTD fed rats. Factors which reduce conducted Na+-uptake (i.e. gramicidin and harmaline) will blunt this augmented uptake. 2. Na+-taurine symport is operating by means of a 2Na+-Cl--taurine mechanisms. Thus, blocking Cl- uptake (furosemide and anion inhibitors) will blunt the adaptive response and taurine will enhance 36Cl-uptake. 3. The growth promoting phorbols and diacylglycerol, which increase Na+-H+ antiport and Na+-K-2Cl symport, will enhance Na+ taurine and the adaptive response. 4. The adaptive response is expressed in immature animals, aged 14, 21 and 28-days but not in 7-day-old rats. This failure to detect changes in BBMV uptake of taurine relates to abnormal 22Na uptake by membranes from young rats. 5. Despite the adaptive response in young rats, they continue to excrete more taurine than older rats even on the LTD (5% vs. 1%). This taurinuria of immaturity relates to decreased permeability at the basal-lateral membrane. 6. Increased Na+-taurine symport could represent synthesis of new transport protein or increased of efficiency of existing symport activity. By the use of one and two dimensional polyacrylamide electrophoresis and fluorescent transport probes, the hypothesis to be tested is that enhanced uptake in rats fed the LTD represents increased symport activity.
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