摘要:

Guanidinoacetic acid (GAA), a precursor of creatine, is an essential substrate for muscle energy metabolism, and synthesized by glycine-amidinotransferase (transamidinase) mainly in the kidney. Since the intranephron distribution of transamidinase activity has never been quantified yet, the purpose of this study is to provide evidence about the localization of transamidinase activity using microdissected individual nephron segments. Synthesized GAA was separated by HPLC and detected fluorometrically after reacting with 9,10-phenanthrenequinone. Results obtained were as follows. (1) Transamidinase activity was distributed only in the first (S1) and the second (S2) portion of the proximal tubule Si being significantly higher than S2. (2) In S2, arginine and glycine were better substrates for GAA synthesis than canavanine and glycine. These results clearly indicate that GAA is synthesized in definite portions of the proximal tubule, and would be transported to the liver for further creatine production.

ISSN:1420-4096    

DOI:10.1159/000173449

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The present study was designed to test whether tubular carbon dioxide production from the carbon skeleton of uniformly 14C-labelled glutamine exhibits quantitative and qualitative segmental heterogeneity. Our results show that CO2 production from glutamine in the proximal convoluted tubule (PCT) was dependent on substrate concentrations and is saturable at 10-4M of glutamine. Glutamine oxidation was demonstrable in all nephron segments examined. The PCT is the quantitatively predominant site of glutamine oxidation. Intermediate nephron segments, however, such as the thick ascending limb (MAL) and the distal convoluted tubule possess a significant capacity for glutamine oxidation, particularly when examined in terms of tubular protein content. Modulation of glutamine oxidation by extracellular pH was segment specific. Stimulation by acidosis and inhibition by alkalosis were observed in the PCT while carbon dioxide production from glutamine in the MAL was pH-insensitive. Glutamine oxidation was closely linked to sodium transport and greatly decreased by inhibition of Na-K-ATPase. In both the PCT and MAL, glutamine oxidation was inhibited by high extracellular potassium concentrations and in the PCT enhanced by extracellular hypokalemia. N-Ethyl maleiamide, an inhibitor of proton ATPase, led to almost complete cessation of CO2 production from the substrate in both PCT and MAL. Acetazolamide, an inhibitor of carbonic anhydrase, led to a partial reduction in carbon dioxide formation in the PCT, but did not affect glutamine oxidation in the MAL. We conclude that segmental qualitative heterogeneity characterizes oxidation of the carbon skeleton of glutamine with proximal segments showing the predictable effects of pH changes and carbonic anhydrase inhibition. The MAL appears to be nonmodulating.

ISSN:1420-4096    

DOI:10.1159/000173450

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The relationship between fractional sodium excretion (FENa) and fractional lithium excretion (FELi) was determined in Munich-Wistar rats with intact capsules (control, n = 16), and in rats with acute bilateral renal decapsulation (n = 16) during hydropenia and acute saline volume expansion. In response to volume expansion, the glomerular filtration rate increased significantly in both decapsulated and intact groups but was similar in the two groups of rats at the same period. The FENa and FELi increased significantly from 0.49 ± 0.10 and 20.09 ± 1.76% to 1.71 ± 0.20 and 34.14 ± 2.82% in control rats with volume expansion. In decapsulated rats, FENa and FELi were 0.17 ± 0.03 and 11.64 ± 1.39% during control and increased to 1.04 ± 0.21 and 26.23 ± 1.17% during volume expansion. The FELi and FENa were significantly greater in control rats compared with decapsulated rats during both control and volume expansion periods. The lower FELi in bilateral renal decapsulation suggests reduced delivery of sodium from the proximal

ISSN:1420-4096    

DOI:10.1159/000173451

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Isoproterenol, a β-adrenoreceptor agonist, decreases urinary phosphate (Pi) excretion; however, plasma phosphate concentration also decreases. The purpose of the present study was to determine the effect of isoproterenol infusion on phosphate reabsorption with concomitant phosphate infusions and in the presence and absence of parathyroid hormone (PTH). Clearance experiments were performed on male Sprague-Dawley rats which were acutely thyroparathyroidectomized (TPTX) and successive infusions of phosphate (1, 2, and 3 µmol/min) were used to determine the maximal tubular capacity of phosphate reabsorption (TmPi) factored for the glomerular filtration rate (GFR) in four groups of rats. In the saline-infused control group the Tmpi/GFR was 2.87 ± 0.19 µmol/ml (n=8). When isoproterenol was infused intravenously at a rate of 0.005 mg/kg/min, urinary cAMP excretion was significantly increased and the TmPi/GFR was 3.53 ± 0.17 µmol/ml (n=10, p < 0.05). In the PTH-infused group (33 U/kg bolus followed by a sustaining infusion of 1 U/kg/min) Tmpi/GFR was 1.69 ± 0.15 µmol/ml (n=9). Coadministration of isoproterenol and PTH significantly increased the TmPi/GFR to 3.25 ± 0.64 µmol/ml (n=9). Basal cAMP excretion was similar in both groups. These results demonstrate that the stimulation of renal β-adrenoreceptors by isoproterenol infusion markedly increases phosphate reabsorption and reverses the decrease in the maximal tubular capacity of phosphate reabsorption induced by PT

ISSN:1420-4096    

DOI:10.1159/000173452

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding nonlithium pretreated groups were generated. When comparing all lithium treated versus nonlithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged. Glomerular hyperfiltration induced by HP, NX or HP+NX for 8 weeks was unable to accelerate progression of uremia in this particular model of chronic renal failure. However, it cannot be excluded that more prolonged exposure to HP and/or NX would have modified the renal parameters differently.

ISSN:1420-4096    

DOI:10.1159/000173453

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Sodium and water excretion were studied by standard clearance techniques in three experimental models where renal mass was reduced by superficial cortical necrosis (CN) or ischemic segmental infarction (SI). During hydropenia either CN or SI were able to conserve and regulate sodium to a very similar degree. After expansion of extracellular volume, CN reabsorbed less sodium and water than SI. In free-water clearance (Ch2o) experiments, the ‘apparent distal’ sodium delivery was higher in CN than in SI, suggesting a decreased sodium and water reabsorption in the proximal tubules of juxtamedullary nephrons (JM). Both kidneys had similar Ch2o when factored for inulin clearance but when Ch2o was corrected for ‘apparent distal’ sodium delivery it was lower in CN than in SI, demonstrating an incapacity of JM to dilute urine. CN also showed less capacity to reabsorb free water than SI. Thus, the use of CN and SI within the same animal was useful to study functional differences between superficial and juxtamedullary nephrons. The present study also suggests that the kidney with superficial CN was unable to perform maximal urine dilution and concen

ISSN:1420-4096    

DOI:10.1159/000173454

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173455

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000317498

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000317499

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173456

出版商:S. Karger AG    

年代:1992

数据来源: Karger