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At least 73 records · Page 4Linked to original sources
PubMed1978

Chemical induction of p-aminohippuric acid transport in renal cortical slices from adult and immature rabbits.

Fourteen-day-old and adult rabbits received procaine penicillin G (PEN), 450,000 U/kg s.c., every 12 hours for a total of four doses or phenobarbital-Na (PHB), 40 mg/kg i.p., once daily for 3 days, or 3-methylcholanthrene (3MC), to 20 mg/kg i.p., once daily for 3 days. Twenty-four hours after the final treatment the animals were killed and the kidneys were removed for analysis of enzymatic activities and p-aminohippuric acid (PAH) transport capability. PEN, PHB and 3MC had no effect on PAH transport in slices from adult rabbits but significantly increased PAH transport in slices from 14-day-old rabbits. Aryl hydrocarbon hydroxylase activity was enhanced in both adult and 2-week rabbit kidneys by 3MC while biphenyl-4-hydroxylase activity was enhanced in 2-week and adult rabbit kidneys by PHB. Epoxide hydratase was unaffected by all three treatments. 3MC increased gluthione-S-aryltransferase (ligandin) activity in 2-week but not adult kidneys. Induction of PAH transport in 14-day-old rabbits does not appear to be related to stimulation of microsomal enzymes or glutathione-S-aryltransferase activity in the kidney. Although they are not considered to be substrates for renal organic anion transport, PHB and 3MC resemble PEN in their ability to induce PAH transport in renal cortex of immature but not adult rabbits.

Aging↗
PubMed1989

Differential effects of the degree of renal damage on p-aminohippuric acid and inulin clearances in rats.

Kidney disease is generally thought to affect all segments of a nephron equally. Bricker and co-workers first proposed this as the Intact Nephron hypothesis in 1971, and evidence to date has usually supported this hypothesis. However, most supporting studies have involved severe renal failure, which may not be suitable to differentiate effects on functional sites or to test the hypothesis. The work included here examines the effects of limited renal failure on two separate functions of the nephron: glomerular filtration, as measured by inulin clearance and proximal tubular organic anion secretory function, as measured by p-aminohippuric acid (PAH) clearance. Renal failure was induced in rats by intravenous administration of uranyl nitrate, a nephrotoxin. Doses used were 0.3, 1.0, and 3.0 mg/kg rat body weight. Five days later, rats were given an intravenous infusion of PAH and inulin. Renal clearance of each compound was calculated. Results obtained in these experiments show that, at the lowest uranyl nitrate dose, PAH clearance was significantly decreased but inulin clearance was not. The ratio of CLPAH/CLIN was decreased from 2.55 in control rats to 1.21 in rats given the low dose of nephrotoxin. At higher uranyl nitrate doses, both clearance rates were significantly decreased and the ratio of CLPAH/CLIN remained close to 1.0. These results indicate that the active transport functions of the nephron can be differentiated from passive transport functions. Caution should be exercised in extrapolating renal disease changes in active renal secretion to changes in passive renal elimination and the reverse.

Aminohippuric Acids↗
PubMed1979

[Investigations on 131I-hippurate-clearance in obstructive-uropathy; extraction of para-aminohippuric acid and 131I-hippurate in the acutely obstructed canine kidney (author's transl)].

The results of more recent clinical and experimental investigations have thrown doubt on the usefulness of determining the individual 131I-hippurate clearance for evaluation of the function of acutely obstructed kidneys. There is a significant difference (5% level) between the kidney performance determined with external measurement on the one hand and with PAH and 125I-hippurate clearance in the steady state on the other. With the steady state method, the restriction of function to be expected in consequence of urinary obstruction is demonstrated, whereas with simultaneous measurement with catheterless 131I-hippurate clearance, an increase in function is detected. In the clearance studies carried out in the conventional way with PAH and 125I-hippurate, it was difficult to determine quantitatively the urine produced during urinary obstruction. The renal extraction of p-aminohippuric acid and 131I-hippurate was therefore determined in simultaneous measurement in six dogs before and after acute urinary obstruction with a constant plasma level of the test substances. The results obtained with this very elaborate method which is, however, independent of urine collection show that an acute urinary obstruction leads to a decrease of renal extraction both of PAH and of 131I-hippurate. Since with conventional clearance, the measurement result is proportional to the amount of substance excreted with the urine, a restriction of function must also result with the steady state methods in determining the performance of acutely obstructed kidneys. The results of the extraction investigations hence confirm the results of the clearance studies mentioned. In addition, they show that the "increase" of renal performance immediately after an experimentally induced urinary obstruction repeatedly found with catheterless determination of 131I-hippurate-clearance cannot be explained by a different kinetic behavior of PAH and 131I-hippurate in the acutely obstructed kidney.

Acute Disease↗
PubMed1976

Transport of p-aminohippuric acid by plasma membrane vesicles isolated from rat kidney cortex.

Basal-lateral plasma membrane vesicles and brush border membrane vesicles were isolated from rat kidney cortex and the uptake of p-aminohippuric acid (PAH) into these vesicles was studied by Millipore filtration techniques. Both membrane preparations take up PAH into an osmotically reactive intravesicular space. The transport across the brush border membrane seems to involve only simple diffusion whereas in the basal-lateral plasma membrane in addition a specific transport system exists which is inhibited competitively by probenecid. The apparent affinity of this transport system for PAH is 5.4 X 10(-4) M and for probenecid 5.4 X 10(-5) M. PAH uptake into basal-lateral plasma membrane vesicles is influenced by alteration of the membrane potential. Maneuvers which render the intravesicular space more positive--as for example replacement of chloride by sulfate in the presence of a sodium gradient directed into the vesicles and addition of valinomycin in the presence of a potassium gradient directed into the vesicles--stimulate the uptake of PAH. Replacement of a sodium chloride gradient by a sodium thiocyanate gradient reduces the uptake probably by reducing the inside positive membrane potential. In the absence of salt gradients anion replacement and replacement of sodium by potassium does not affect PAH transport by basal-lateral plasma membranes. These results suggest that in isolated basal-lateral membranes transfer of PAH across the membrane is accompanied by a transfer of negative charge. They furthermore provide no evidence for the existence of a sodium-PAH cotransport system in this membrane preparation.

Aminohippuric Acids↗
PubMedDate not supplied

A non-radioactive iothalamate and p-aminohippuric acid high-performance liquid chromatographic method for simultaneously measuring glomerular filtration rate and renal blood flow in the rat.

A high-performance liquid chromatographic (HPLC) assay method has been developed for the quantitative determination of iothalamate and p-aminohippuric acid (PAH) concentrations in serum and urine samples in the male rat. Glomerular filtration rate (GFR) was measured as clearance of iothalamate, while effective renal blood flow (ERBF) was measured as clearance of PAH. The method is simple, rapid and sensitive and detects iothalamate and PAH in rat serum and urine following administration of bolus doses and continuous infusions of iothalamate and PAH. Samples of serum and urine were deproteinized with two volumes of acetonitrile containing the internal standard, and an aliquot chromatographed on a C18 reversed-phase column. The mobile phase was comprised of 0.1 M sodium phosphate with 1.2 mM tetrabutylammonium phosphate: methanol, 85:15 (v/v), at a flow rate of 1.0 mL/min. The analytical column eluate was monitored with a UV detector at 254 nm with quantitation achieved using peak-height ratios. The precision of the method was 6.6 and 3.6% for iothalamate in serum and urine, and 5.6 and 4.9% for PAH in serum and urine, respectively. The lower limit of quantitation was 0.63 microgram/mL for iothalamate and 1.25 microgram/mL for PAH in serum, and 3.1 microgram/mL for iothalamate and 1.5 microgram/mL for PAH in urine. Recovery of iothalamate from serum and urine was 99.9 and 93.5%, respectively. Recovery of PAH from serum and urine was 99.8 and 92.6%, respectively. The present study demonstrated that non-radioactive iothalamate and PAH can be measured simultaneously using a HPLC assay to measure GFR and ERBF in the male rat.

Animals↗
PubMed2000

p-aminohippuric acid transport at renal apical membrane mediated by human inorganic phosphate transporter NPT1.

Organic anions are secreted into urine via organic anion transporters across the renal basolateral and apical membranes. However, no apical membrane transporter for organic anions such as p-aminohippuric acid (PAH) has yet been identified. In the present study, we showed that human NPT1, which is present in renal apical membrane, mediates the transport of PAH. The K(m) value for PAH uptake was 2.66 mM and the uptake was chloride ion sensitive. These results are compatible with those reported for the classical organic anion transport system at the renal apical membrane. PAH transport was inhibited by various anionic compounds. Human NPT1 also accepted uric acid, benzylpenicillin, faropenem, and estradiol-17beta-glucuronide as substrates. Considering its chloride ion sensitivity, Npt1 is expected to function for secretion of PAH from renal proximal tubular cells. This is the first molecular demonstration of an organic anion transport function for PAH at the renal apical membrane.

Anions↗
PubMed2004

Renal secretion of the antiviral nucleoside analog AM188 is inhibited by probenecid, p-aminohippuric acid, and cimetidine in the isolated perfused rat kidney.

PURPOSE: To investigate the effects of potential inhibitors of membrane transport on the tubular secretion of AM188, an antiviral guanosine analog, in the isolated perfused rat kidney (IPK). METHODS: AM188 was administered to the IPK perfusate as a bolus/infusion regimen. In inhibitor groups, probenecid, p-aminohippuric acid (PAH), cimetidine, or nitrobenzylthioinosine was added to the perfusing medium. RESULTS: In control IPKs, the ratio of renal clearance of AM188 (CLR) to GFR was 7.7 +/- 0.51 (mean +/- SD). The CL(R)/GFR ratio for AM188 was 6.20 +/- 0.41*, 2.85 +/- 0.20*, 1.45 +/- 0.07*, and 0.80 +/- 0.01* when the concentration of probenecid in perfusate was 10, 50, 100, and 1000 microM, respectively (*p < 0.05 compared to control group); the ratio was 7.71 +/- 0.38, 6.02 +/- 0.42*, 1.71 +/- 0.15*, and 0.91 +/- 0.07* for the PAH group and 6.42 +/- 1.70*, 5.33 +/- 1.53*, 3.16 +/- 0.81*, and 1.21 +/- 0.20* for the cimetidine group when the concentrations were 10, 100, 1000 and 10,000 microM, respectively; and the ratio was 5.33 +/- 0.21* when the concentration of nitrobenzylthioinosine was 5 microM. CONCLUSIONS: These results suggest that renal tubular secretion of AM188 involves organic anion and cation transport systems.

Animals↗
PubMed1975

Binding of N1-methylnicotinamide and p-aminohippuric acid to a particulate fraction from dog kidney.

The active secretion of organic ions by the kidney may be described by the following models: 1)binding to a carrier protein and 2) a translocation process across the membrane. The feasibility of such a model was tested by measuring binding of either an organic cation, N1-methylnicotinamide (NMN) or an organic anion p-aminohippuric acid (PAH) to particulate material obtained from dog renal cortex tissue. The method employed was one in which the bound and free forms of the ligand were separated by centrifugation through a gel matrix. Binding of NMN and PAH was found to be tissue specific. In addition, binding was pH, time, temperature, protein-concentration and ligand-concentration dependent. Saturation of binding for either ligand was observed at concentrations greater than 50 mM, suggesting low affinity. Interestingly, a positive cooperative effect was observed for binding of either NMN or PAH to the particulate material. Although binding was associated only with particulate material, the binding proteins were released from the membrane system(s) by treatment with the nonionic detergent Lubrol WX. These studies show that NMN and PAH binding share many features in common but that the two processes are independent of each other. The results are consistent with, but do not prove, the model.

Aminohippuric Acids↗
PubMed1997

Effects of the novel thromboxane (TXA2) receptor antagonist linotroban on inulin and para-aminohippuric acid clearances in the conscious male and female rat.

This paper reports the results of experiments designed to determine the effect of linotroban (CAS 141443-73-4) a selective thromboxane (TXA2) receptor antagonist with novel antithrombotic activity, on renal function in conscious male and female rats. Linotroban was administered subcutaneously at doses of 0, 6, 24, 48 and 96 mg/kg/24 h by osmotic minipumps over 6 days. Inulin (Inutest) and para-aminohippuric acid (PAH) clearances were determined on the last day of linotroban treatment. These agents were delivered by a slow release tablet planted s.c. five days after the start of the linotroban treatment. Linotroban did not significantly alter renal functions, although there was a significant difference in GFR (glomerular filtration rate) for male and female rats receiving the highest dose. Linotroban is well tolerated but the difference in renal function between male and female rats at the highest dose may reflect a threshold of renal tolerance.

Acetates↗
PubMedDate not supplied

A comparison of inulin, para-aminohippuric acid, and endogenous creatinine clearances as measures of renal function in neonatal foals.

The glomerular filtration rate (GFR) was estimated in eight full-term neonatal foals by the single injection inulin plasma clearance method at two days of age, the continuous infusion plasma and urinary clearance methods at three days of age, and the 12-hour endogenous creatinine clearance method at four days of age. The effective renal plasma flow (ERPF) was estimated simultaneously by the single injection para-aminohippuric acid (PAH) plasma clearance method in the eight two-day old foals and the continuous PAH infusion plasma and urinary clearance method in the eight three-day old foals. The GFR (+/- 1 SEM), as determined from the single injection plasma clearance method, was 2.30 +/- 0.34 mL/kg/min; by continuous infusion plasma clearance 2.56 +/- 0.30 mL/kg/min; by continuous infusion urinary clearance 2.82 +/- 0.32 mL/kg/min; and by 12-hour endogenous creatinine clearance 2.81 +/- 0.55 mL/kg/min. Effective renal plasma flow (+/- 1 SEM) measured by the single injection plasma clearance method was 15.22 +/- 1.5 mL/kg/min, by continuous infusion plasma clearance was 18.21 +/- 2.0 mL/kg/min. and by continuous infusion urinary clearance it was 11.95 +/- 1.9 mL/kg/min. The results of these methods were not statistically different. On a per kilogram body weight basis, the full-term neonatal foal's GFR and ERPF was determined to be comparable with adult equine GFR and ERPF.

Animals↗
PubMed2003

Contribution of organic anion transporter 3 (Slc22a8) to the elimination of p-aminohippuric acid and benzylpenicillin across the blood-brain barrier.

The role of rat organic anion transporter 3 (rOat3; Slc22a8) in the efflux transport at the blood-brain barrier (BBB) was characterized. The expression of rOat1, rOat2, and rOat3 in the brain capillary endothelial cells (BCEC) was examined using reverse transcription-polymerase chain reaction analysis, which showed that there was no expression of rOat1 or rOat2, but moderate expression of rOat3. The expression of rOat3 in the BCEC was further confirmed by Western blotting. Immunohistochemical staining showed that rOat3 is located on the abluminal and, possibly, luminal membrane of the BCEC. The contribution of rOat3 to the efflux of para-aminohippuric acid (PAH) and benzylpenicillin (PCG), substrates of rOat3, from the cerebrum into the blood circulation across the BBB was evaluated using the Brain Efflux Index method. PAH and PCG were eliminated from the cerebrum with rate constants of 0.039 and 0.043 min-1, respectively, and the elimination was saturated at high substrate concentrations. Taking account of the dilution in the brain, the Km values for the elimination of PAH and PCG were estimated to be 168 and 29 micro M, respectively. The efflux of PAH and PCG across the BBB was inhibited in a dose-dependent manner by unlabeled PCG and PAH, respectively. The Ki value of PAH for the efflux of PCG was 106 micro M and that of PCG for the efflux of PAH was 58 micro M. These values were comparable with their Km values, suggesting that they share the same efflux mechanism at the BBB. Furthermore, cimetidine and pravastatin, which are also substrates and inhibitors of rOat3, significantly inhibited the efflux of PAH and PCG from the cerebrum. These results suggest that rOat3 is responsible for the elimination of PAH and PCG from the brain across the BBB.

Animals↗