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At least 1,081 records · Page 60Linked to original sources
PubMed1985

A gamma-aminobutyric acid-specific transport mechanism in mammalian kidney.

We describe high-affinity, sodium-dependent transport of gamma-aminobutyric acid in slices exposing basal lateral membranes and brush-border membrane vesicles prepared from rat renal cortex. In the presence of aminooxyacetic acid, to block gamma-aminobutyric acid oxidation, uptake into the intracellular space of slices was saturable (apparent Kt, 26 +/- 4 microM, mean and S.E.) and concentrative (steady-state distribution ratio at 50 microM gamma-aminobutyric acid, 47.7 +/- 2.4, mean and S.E.). Brush-border membrane vesicles accumulated gamma-aminobutyric acid in the presence of an inward-directed sodium chloride gradient, (apparent Kt, 30-36 microM) with the peak of 'overshoot' at 10 min. Uptake by vesicles responded to manipulation of the transmembrane potential gradient with valinomycin or impermeant anion. beta-Alanine inhibited gamma-aminobutyric acid transport by slices and brush-border membrane vesicles; inhibitors of neuronal-type gamma-aminobutyric acid transport (e.g., nipecotic and diaminobutyric acids) did not. An 'ABC test' indicated that gamma-aminobutyric acid and beta-alanine do not share a single carrier in either the brush-border or basal-lateral membrane of renal cortex. Influx of gamma-aminobutyric acid into brush-border membrane vesicles, at transequilibrium NaCl, was stimulated by trans-gamma-aminobutyric acid but not by trans-taurine. Ion gradient-driven gamma-aminobutyric acid co-transport was unaffected in freeze-thawed brush-border membrane vesicles; this treatment abolished beta-alanine and taurine co-transport. We conclude that rat kidney membranes (brush-border and basal-lateral) possess a gamma-aminobutyric acid-preferring, high-affinity transport mechanism.

Animals↗
PubMed1992

Urate excretion by the cat kidney.

1. The renal handling of urate by the cat kidney was investigated during continuous infusion of urate. 2. Fractional urate excretion (FE(UA)) in cats was 0.57 +/- 0.04, indicating net reabsorption of urate. In contrast, FE(UA) in rabbits was 1.76 +/- 0.08, reflecting net secretion of urate. 3. Fractional PAH excretion (FE(PAH)) was 3.94 +/- 0.26 in cats and 4.12 +/- 0.76 in rabbits, showing net secretion in both species. 4. FE(UA) in cats was dependent on urine flow, but was independent of plasma urate concentration. 5. The urate excretion in cats was enhanced by probenecid, but was insensitive to PAH and PZA. 6. The PAH excretion in cats was reduced by probenecid, but was unaltered by urate and PZA. 7. These results indicate that urate is handled in the cat kidney by a unique transport system which is distinct from that for organic anions.

Animals↗
PubMed1989

Cisplatin: nephrotoxic action in vertebrates and its prevention.

1. The kidney of frog and black sculpin appeared to be much less sensitive to the toxic action of CP in comparison with rat and pigeon. 2. The impairment of renal function after CP administration resulted in increased serum urea in rat, uric acid in pigeon and magnesium in black sculpin. 3. Kidney swelling is important feature of CP nephrotoxicity in rat and pigeon but not in frog and fish. 4. Pretreatment with choline chloride, PAH, furosemide and ethacrynic acid reduced the nephrotoxic action of CP in rat but did not prevent the accumulation of platinum in renal tissue which appeared to be a function of the dose injected to investigated animals.

Animals↗
PubMed1999

Effect of glucuronidation substrates/inhibitors on N-(3,5-dichlorophenyl)succinimide nephrotoxicity in Fischer 344 rats.

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is an acute nephrotoxicant in rats. Our previous studies have strongly suggested that glucuronide conjugation of NDPS metabolites might be a bioactivation step mediating NDPS nephrotoxicity. In this study, effects of substrates and/or inhibitors of primarily glucuronidation on NDPS nephrotoxicity were examined to explore further the role of glucuronidation in NDPS nephrotoxicity. Male Fischer 344 rats (4-6/group) were administered one of the following intraperitoneal (i.p.) pretreatments (dose, pretreatment time) prior to NDPS (0.4 mmol/kg) or NDPS vehicle (sesame oil, 2.5 ml/kg): (1) no pretreatment; (2) borneol (900 mg/kg, 30 min); (3) eugenol (500 mg/kg per day, 3 days); (4) clofibric acid (400 mg/kg, 15 min before (1/2 dose) and 3 h after (1/2 dose)), or (5) valproic acid, sodium salt (1.0 mmol/kg, 15 min). Following NDPS or NDPS vehicle administration, renal function was monitored at 24 and 48 h. Pretreatment with borneol or eugenol, substrates for ether glucuronidation and sulfation (mainly glucuronidation), afforded complete protection against NDPS nephrotoxicity. Substrates for acyl glucuronidation, clofibric acid or valproic acid, mildly reduced or had little effect on NDPS nephrotoxicity, respectively. These results suggest that ether glucuronide conjugates of NDPS metabolites, rather than acyl glucuronide conjugates, may be the primary ultimate nephrotoxicant species mediating NDPS nephrotoxicity.

Animals↗
PubMed1980

Uptake of gentamicin by separated, viable renal tubules from rabbits.

The proximal renal tubules have a marked affinity for gentamicin; they also are the major site of nephrotoxicity caused by this drug. The uptake of radiolabeled gentamicin in separated, viable renal tubules prepared by enzymatic digestion of rabbit kidneys was studied. The preparations showed rapid initial uptake of gentamicin followed by continued slower uptake. Accumulation was not affected by pH, but was significantly inhibited by ouabain, dinitrophenol, anoxia, and hypothermia in the absence of evident cellular damage. At gentamicin concentrations of greater than 50 microgram/ml in the medium, there was competition for drug uptake. Gentamicin efflux in tubules that were taken from a medium containing antibiotic and placed into antibiotic-free fluid was slow and incomplete. From these data it appears that gentamicin uptake by separated renal tubules occurs by a process that requires metabolic energy; thereafter, the drug resides in a poorly exchangeable cellular pool.

Aminoglycosides↗
PubMed1980

Activity of a new high efficiency diuretic in man: piretanide (HOE 118).

1 The pharmacological actions of piretanide, a new high efficiency diuretic, were studied in sixteen patients with GFR (inulin clearance) varying from 0.1--2.5 ml/s. 2 After hydration and following two control periods, a single dose of 6 mg piretanide was ingested. Thereafter, urine was collected every 30 min for 2 h and every hour for the next 4 h. Fluid losses were replaced. 3 The following measurements were made: urine flow rate, clearances of inulin, PAH, urea, creatinine, uric acid, osmolar and free water clearances, excretion rates of sodium, chloride, potassium, calcium, phosphate, bicarbonate, ammonium, titratable acidity and urine pH. 4 Main results showed piretanide was efficient in the group with normal GFR (inulin clearance greater than 1.5 ml/s) and in the group with slightly decreased GFR (1.0 less than inulin clearance less than 1.4 ml/s), in terms of diuresis, natriuresis, kaliuresis and calciuresis. It was inefficient in the group with severe renal insufficiency (inulin clearance less than 0.3 ml/s). 5 Free water clearance showed preservation of diluting ability to a large extent. 6 In the three groups, no significant change in inulin clearance and PAH clearance occurred.

Adult↗
PubMed1982

Net urate reabsorption in the Dalmatian coach hound with a note on automated measurement of urate in species with low plasma urate.

A progressive reduction of renal blood flow and glomerular filtration rate induced by the stepwise clamping of a Goldblatt clamp increases the urate over creatinine clearance ratio from 1.2 to 1.9 in normal urate-secreting Dalmatian dogs. These clearance data support the existence of a predominant postreabsorptive secretory flux of urate in the normal Dalmatian dog. In contrast, in Dalmatians loaded with pyrazinoic acid which suppresses urate secretion, net reabsorption of urate is unmasked and the urate over creatinine clearance ratio decreases with the progressive reduction in glomerular filtration rate (down to 0.44). It is concluded that the net reabsorption of urate measured by conventional clearance techniques after pharmacologic depression of the urate secretory flux probably reflects true urate reabsorption in the nephron of this species.

Absorption↗
PubMed1978

Comparison of different methods of clearance determination.

Clearance determination by compartmental analysis of hippurate renograms was compared in 30 cases to the conventional PAH and to the partly shielded whole body counting technique. Good correlations between compartmental analysis and PAH method (r = 0.96) as well as the whole body technique (r = 0.94) were found. Correlation between PAH and whole body method was not always satisfactory (r = 0.85). In an additional study influence of greater count rates become obvious: correlation coefficients increase from 0.89 (131I-hippurate, n = 97) to 0.95 (123I-hippurate, n = 38). Determination of the divided clearance correlates well (r = 0.95). Using 123I-hippurate all the information available by radioisotopic kidney investigations can be obtained in a one-step procedure.

Aminohippuric Acids↗