Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sulfate transport studies were carried out in secondary cultures of epithelial cells isolated from the human ureter. Results demonstrate the presence of carrier-mediated SO4(2-) transport as supported by three lines of evidence: 1) saturation kinetics, 2) substrate specificity, and 3) inhibition by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). The DIDS-insensitive component of SO4(2-) transport was markedly lower than the DIDS-sensitive component and was not affected by changes in extracellular pH (pHo) or Cl- concentration. The mechanism of this DIDS-insensitive component is not clear. The DIDS-sensitive component of SO4(2-) uptake was a saturable function of the extracellular sulfate concentration ([SO4(2-)]o). Increasing the extracellular chloride concentration ([Cl-]o) inhibited DIDS-sensitive SO4(2-) uptake competitively. Taken together with the fact that increasing [Cl-]o stimulated SO4(2-) efflux, these results suggest that SO4(2-) uptake in uroepithelial cells occurs via SO4(2-)-Cl- anion exchange. Cis-inhibition studies with a variety of anions indicate that this anion-exchange system may be shared by S2O3(2-) and MoO4(2-) but not by NO3- and H2PO4-. SO4(2-) uptake was stimulated at decreasing pHo with a pK approximately 7.4. Decreasing pHo from 7 to 6 lowered the apparent Michaelis constant significantly but had no significant effect on kcat, suggesting that protons may increase the affinity of the SO4(2-) transporter for SO4(2-). SO4(2-) efflux was inhibited at low pHo and was stimulated by increasing [Cl-]o. This study is the first to demonstrate an ion transport process in epithelial cell cultures isolated from the human ureter. In contrast to epithelial cells from the upper urinary tract, no Na(+)-dependent SO4(2-) transport could be demonstrated in these lower urinary tract epithelial cells. In conclusion, the major mechanism for SO4(2-) transport in ureteral epithelial cells is a carrier-mediated, DIDS-sensitive, pHo-sensitive SO4(2-)/Cl- anion-exchange mechanism. These studies suggest that varying [SO4(2-)]o and [Cl-]o or pHo in the ureteral lumen will affect SO4(2-) influx and efflux and may influence the size of the intracellular pool of SO4(2-) available for macromolecular sulfation in these cells.
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PMID:Carrier-mediated sulfate transport in human ureteral epithelial cells cultured in serum-free medium. 195 76

Glycerol acute renal failure (ARF) was examined to see if it alters theophylline (Th) neurotoxicity in rats. Concentrations of Th in serum, cerebrospinal fluid and in brain at seizure onset were similar in control and ARF rats infused with Th. Thus, glycerol ARF fails to alter Th neurotoxicity, an effect similar to that noted previously with uranyl nitrate but not with ureter ligation.
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PMID:Theophylline neurotoxicity is unaffected by glycerol-induced renal failure. 208 97

The purpose of this investigation was to determine if the pharmacodynamics of the central nervous system stimulant pentylenetetrazol (PTZ) are altered in renal dysfunction. Female rats subjected to bilateral ureteral ligation (with sham-operated controls) or injected with uranyl nitrate (with saline injected controls) were infused intravenously with PTZ until the onset of either a minimal (myoclonic jerk) or maximal (tonic hindlimb extension) seizure. Neither chemically nor surgically induced renal dysfunction caused a change in the concentrations of PTZ in CSF, serum, or brain at onset of minimal seizures. When PTZ was infused to onset of maximal seizures, the rats with chemically induced renal dysfunction required higher concentrations, whereas the ureter-ligated rats convulsed at lower concentrations of PTZ than did the corresponding control animals. Thus, the effects of experimental renal dysfunction on the convulsant action of PTZ are dependent on both the disease model and the endpoint used for the pharmacodynamic measurement. Apparently, renal dysfunction did not affect the PTZ-induced seizure threshold, but inhibited the spread of seizures. The increased sensitivity of ureter-ligated rats may be due to their pronounced retention of water, since water loading is known to increase seizure susceptibility.
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PMID:Kinetics of drug action in disease states. XXXIII: Disparate effects of pentylenetetrazol in rats as a function of renal disease model and pharmacologic endpoint. 271 36

The renal disposition of insulin in acute renal failure has not been evaluated. We used the isolated perfused rat kidney to test the hypothesis that acute renal failure (ARF) decreases renal insulin clearance. We used warm ischemia for 45 min, uranyl nitrate 5 mg/kg, ureter ligation, and nonfiltering kidneys as methods of inducing ARF. Comparisons were made with normal control kidneys. The concentrations of insulin in perfusate and urine was determined by radioimmunoassay. Acute renal failure caused significant reductions in glomerular filtration rate, sodium and potassium reabsorption, and an increased urine pH. Warm ischemia and uranyl nitrate toxicity caused a 50% decrease in the renal clearance of insulin. Nonfiltering kidneys cleared insulin at a rate 90% decreased from controls. Ureteral ligation caused a 32% decrease in insulin clearance. Filtration was necessary for insulin to be cleared from perfusate. We conclude that ARF decreased renal insulin clearance through a decrease in insulin uptake from both the tubular lumen and peritubular surface.
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PMID:Effect of acute renal failure on insulin disposition in the isolated perfused rat kidney. 331 99

Theophylline, the bronchodilating agent, can cause life-threatening, generalized seizures when plasma concentrations exceed the usual therapeutic concentration range. However, the plasma concentrations of theophylline associated with this neurotoxic effect vary widely between patients. To determine the reasons for the wide variation, and thereby to facilitate prevention or early treatment of theophylline-induced neurotoxicity, an animal model of theophylline-induced seizures was developed and has now been used to determine the effect of experimental renal failure on the concentrations of theophylline that cause convulsions. Adult female rats were subjected to bilateral ureteral ligation or injected with uranyl nitrate to produce renal failure or dysfunction. Sham-operated and saline-injected rats, respectively, served as controls. Theophylline was infused i.v. at either 1.03 or 2.06 mg/min until the onset of maximal seizures. Renal failure due to ureter ligation was associated with a substantial reduction of the dose of drug required to produce seizures, the concentrations of total and free (unbound) theophylline in serum and the concentrations of theophylline in the brain and cerebrospinal fluid at onset of seizures. The concentrations of theophylline metabolites were very low and did not account for the enhanced neurotoxicity. No apparent change in the neurotoxicity of theophylline was observed in rats with uranyl nitrate-induced renal dysfunction. The results of the investigation on ureter-ligated rats are consistent with recent clinical findings of a higher incidence of theophylline-induced neurotoxicity in azotemic patients. The experimental methodology may therefore be suitable for the prospective identification of other potential clinical risk factors for theophylline neurotoxicity.
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PMID:Kinetics of drug action in disease states. XVIII. Effect of experimental renal failure on the pharmacodynamics of theophylline-induced seizures in rats. 380 13

This investigation was designed to determine if renal dysfunction is associated with an increased sensitivity to the CNS depressant effect of ethanol. Adult female Lewis rats were given injections of either 2 or 5 mg/kg of uranyl nitrate (saline for controls) or had both ureters ligated (sham operation for controls) to provide different experimental models of renal dysfunction. Normal and renal dysfunction (ureter-ligated) rats were infused i.v. with ethanol at rates of 8.1, 16.3 or 32.6 mg/min; concentrations of ethanol in cerebrospinal fluid, serum and brain at onset of loss of righting reflex were independent of infusion rate in both groups, indicating rapid equilibration of ethanol between the sampling sites and the biophase. Ethanol concentrations in cerebrospinal fluid at onset and offset (after approximately 110 min of sleep) of loss of righting reflex were not significantly different, reflecting negligible acute tolerance development under the experimental conditions. Ethanol concentrations at onset of loss of righting reflex in cerebrospinal fluid, serum and brain of rats with severe renal dysfunction (5 mg/kg of uranyl nitrate-treated and ureterligated groups) were slightly but statistically significantly lower than in normal controls. This difference was relatively much smaller than the difference in phenobarbital concentrations observed in a similar preceding study, which is consistent with the different mechanisms of action of alcohols and barbiturates.
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PMID:Kinetics of drug action in disease states. VII. Effect of experimental renal dysfunction on the pharmacodynamics of ethanol in rats. 387 54

Hepatocytes isolated from livers of rats with various models of acute uremia (binephrectomy, ureter ligation, uranyl nitrate-induced, or ischemic ARF) were incubated with glucagon, adrenalin, or cyclic AMP using serine as a substrate. A marked increase in glucose production was observed in the hepatocytes of uranyl nitrate-treated, binephrectomized, and ureter-ligated rats compared to starved controls or sham-operated animals. This effect was strengthened in the presence of glucagon, adrenaline, or cyclic AMP. In liver cells of binephrectomized and ureter-ligated animals, the production of acetoacetate and beta-hydroxybutyrate was significantly higher than in controls and sham-operated rats. Oxoglutarate and ATP production was only enhanced after ureter ligation. The correlation between glucose concentration and the cytosolic redox state was different in control and sham-operated rats than in either uremic group. This study confirms earlier investigations of a key role of serine in carbohydrate metabolism in acutely uremic rats.
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PMID:Effect of serine on gluconeogenic ability of hepatocytes in acute uremia. 633 Apr 26

Liver cells were prepared from untreated controls, rats with various models of acute uraemia (uranyl nitrate-treated, bilaterally nephrectomised and ureter-ligated rats, rats with acute ischaemic renal failure) and sham-operated animals. Hepatocyte glucose output, pyruvate utilisation and lactate production were determined in the presence of Krebs-Ringer bicarbonate buffer with different pH values (7.1, 7.4, 7.6) using pyruvate, dihydroxyacetone, serine and fructose as substrates. In the presence of pyruvate and dihydroxyacetone a significant increase of glucose production in hepatocytes from bilaterally nephrectomised and ureter-ligated rats was observed. However, pyruvate-generated glucose production in the hepatocytes of uranyl nitrate-treated animals was unchanged, while a diminished glucose output was seen in the presence of dihydroxyacetone. A marked increase in glucose and lactate production in the presence of serine was observed in the hepatocytes of uranyl nitrate-treated, ureter-ligated and binephrectomised rats. However, lactate production from dihydroxyacetone in the liver cells of uranyl nitrate-treated animals was inhibited. In contrast to other types of uraemia, in acute ischaemic renal failure there is significantly lower hepatocyte glucose production using pyruvate as a substrate, but unchanged glucose generation from dihydroxyacetone or serine.
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PMID:The gluconeogenetic ability of hepatocytes in various types of acute uraemia. 681 Jan 92

The investigation was designed to determine the effect of experimental renal failure on the retention of free (inorganic) sulfate and on the pharmacokinetics of acetaminophen in rats. Adult male Sprague-Dawley rats with renal failure produced by uranyl nitrate treatment or ligation of ureters had much higher serum free sulfate concentrations (about 2 and 5 mM, respectively) than normal animals (about 1 mM). The time-averaged total clearance of a 100-mg/kg dose of acetaminophen was higher in animals with renal failure than in normal rats and was positively correlated with serum free sulfate concentration (r = 0.76, P less than .001). Renal failure had no effect on the total clearance of a 15-mg/kg dose of acetaminophen, apparently because free sulfate was not appreciably depleted by this small dose. A 6-hr infusion of acetaminophen, at 36 mg/kg/hr, produced steady-state plasma concentrations of about 20 micrograms/ml within 2 hr in renal failure (ureter-ligated) animals, whereas in normal animals the plasma concentrations increased continuously to about 100 micrograms/ml at 6 hr. Free sulfate concentrations in serum at the end of the infusion were about 0.2 mM in normal animals and generally greater than 1 mM in the renal failure animals. The rats with renal failure converted most of the administered dose to acetaminophen sulfate, whereas normal animals metabolized much of the drug to acetaminophen glucuronide. These observations demonstrate the important effect of the endogenous free sulfate level in the body on the elimination kinetics and metabolic fate of a drug that is subject to conjugation with sulfate.
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PMID:Effect of experimental renal failure on sulfate retention and acetaminophen pharmacokinetics in rats. 706 93

Scanning electron microscopy, correlated with hematological and clinical biochemical observations demonstrated that cytoplasmic bridges develop between the erythrocytes of sheep in which varying degrees of acute renal dysfunction has been produced by treatment with a toxin (uranyl nitrate) or by surgical ligation of a renal artery or ureter. The presence of cytoplasmic bridges between red blood cells was noted prior to clinical indication of renal dysfunction. Thus, these preliminary studies indicate that the development of cytoplasmic bridges between erythrocytes may be a diagnostic clue for early detection of renal dysfunction.
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PMID:Cytoplasmic bridges between mammalian red blood cells: an early indication of kidney dysfunction. 717 Jun 4


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