scholarly journals Effects of fluorocitrate on renal ammoniagenesis and glutamine metabolism in the intact dog kidney

1979 ◽  
Vol 15 (3) ◽  
pp. 255-263 ◽  
Author(s):  
Edmund Bourke ◽  
Gustavo Frindt ◽  
George E. Schreiner ◽  
Harry G. Preuss
1992 ◽  
Vol 262 (6) ◽  
pp. F1007-F1014
Author(s):  
A. C. Schoolwerth ◽  
B. C. Smith ◽  
K. Drewnowska

To examine the interrelationships of proton compartmentation and ammoniagenesis, experiments were performed in tubules and mitochondria isolated from dog kidney cortex. Tubules were incubated in Krebs-Henseleit buffer at different pH (pHe), and cytosolic pH (pHi) was estimated with the fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Mitochondrial pH (pHm) was determined simultaneously in intact tubules by use of dimethyloxazolidine-2,4-dione. Over the pHe range 6.9-7.7, pHi was similar in control and acidotic dogs and linearly related to pHe. At pHe 7.4 in control tubules. pHm was 7.78 +/- 0.07, and varied little over the pHe range of 7.0-7.7. The pH gradient across the mitochondrial membrane rose at acid pHe. pHm was more alkaline when estimated in tubules from acidotic dogs compared with controls. Ammonium and glucose productions from glutamine were inversely related to pHe and pHi in tubules from both control and acidotic animals and were higher in acidosis. In contrast, ammonium production by isolated mitochondria did not vary as pHe was altered. Enzyme fluxes, calculated from metabolite changes, demonstrated that glutamate dehydrogenase (GDH) flux was altered. Enzyme fluxes, calculated from metabolite changes, demonstrated that glutamate dehydrogenase (GDH) flux was inversely and glutaminase (PDG) flux was linearly related to pHe. Ammonium production was significantly greater in mitochondria from acidotic dogs because of accelerated flux through PDG but not GDH. The present study demonstrates significant difference between proton compartmentation and regulation of ammoniagenesis in kidneys from acidotic dog compared with rat.


1983 ◽  
Vol 210 (2) ◽  
pp. 483-487 ◽  
Author(s):  
D Durozard ◽  
G Baverel

1. The effects of 3-aminopicolinate, a known hyperglycaemic agent in the rat, on glutamine metabolism were studied in isolated dog kidney tubules. 2. 3-Aminopicolinate greatly stimulated glutamine (but not glutamate) removal and glutamate accumulation from glutamine as well as formation of ammonia, aspartate, lactate, alanine and glucose. 3. The increased accumulation of aspartate from glutamine and glutamate, and the inhibition of glucose synthesis from various non-nitrogenous gluconeogenic substrates, as well as the increased accumulation of malate from succinate, support the proposal that 3-aminopicolinate is an inhibitor rather than a stimulator of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in dog kidney tubules. 4. With glutamine as substrate, the increase in flux through glutamate dehydrogenase (EC 1.4.1.3) could not explain the large increase in glutamine removal caused by 3-aminopicolinate. 5. Inhibition by amino-oxyacetate of accumulation of aspartate and alanine from glutamine caused by 3-aminopicolinate did not prevent the acceleration of glutamine utilization. 6. These data are consistent with a direct stimulation of glutaminase (EC 3.5.1.2) by 3-aminopicolinate in dog kidney tubules.


1986 ◽  
Vol 29 (1) ◽  
pp. 68-79 ◽  
Author(s):  
Patrick Vinay ◽  
Guy Lemieux ◽  
André Gougoux ◽  
Mitchell Halperin

1985 ◽  
Vol 248 (4) ◽  
pp. F585-F593
Author(s):  
A. Gougoux ◽  
P. Vinay ◽  
M. Duplain

Studies were performed in anesthetized normal dogs to evaluate the effects of maleate on renal metabolism. Intravenous administration of maleate (50 mg/kg) markedly increased urinary excretion of glutamine, glutamate, alpha-ketoglutarate, alanine, lactate, pyruvate, and citrate. Despite a fourfold rise in renal cortical concentration of alpha-ketoglutarate, glutamine utilization expressed per 100 ml glomerular filtration rate almost doubled following maleate administration, whereas total ammonia production increased threefold, most of this ammonia being diverted into the renal vein. The renal production of alpha-ketoglutarate rose in a spectacular fashion and was almost equal to the renal utilization of glutamine, indicating a metabolic block at the alpha-ketoglutarate dehydrogenase step. Maleate reduced renal alanine production but did not change lactate utilization. These findings suggest that 1) in the intact dog the mitochondrial entry of glutamine is not regulated only by alpha-ketoglutarate; 2) the deamination of glutamate into alpha-ketoglutarate is accelerated by maleate, probably through an impaired mitochondrial NADH production; 3) the resulting decrement in intramitochondrial glutamate concentration deinhibits the phosphate-dependent glutaminase.


Author(s):  
C. Manillier ◽  
P. Vinay ◽  
L. Lalonde ◽  
J. Noel ◽  
A. Gougoux ◽  
...  

1986 ◽  
Vol 251 (5) ◽  
pp. F919-F932
Author(s):  
C. Manillier ◽  
P. Vinay ◽  
L. Lalonde ◽  
A. Gougoux

In vivo the dog kidney responds to metabolic or respiratory acidosis by a marked increment of its ammonia production (expressed per 100 milliliters glomerular filtration rate). This phenomenon is related to a switch from metabolic utilization of nonammoniagenic (lactate) to ammoniagenic (glutamine) substrates to support ATP turnover in the proximal tubules. We have proposed that in vivo the maximum activity of the ammoniagenic process is fixed by the ATP turnover in this segment of the nephron. The maximal glutamine metabolism is reached when 100% of this turnover is supported by glutamine metabolism. We have studied how these concepts apply to the adaptation of glutamine metabolism and ammonia production to a low pH in vitro using proximal tubules of dogs incubated when one (lactate or glutamine) or several (glutamine plus lactate or plus palmitate) substrates are provided. At pH 7.4 glutamine alone supports already 71-76% of the tissue ATP turnover (minimal and maximal values). With acidification this fraction rises to nearly 87-94%, but this increases only modestly the ammonia production. Reducing the ATP turnover with ouabain at pH 7.4 decreases the absolute glutamine utilization, which now supports only 45-50% of the ATP turnover. Again acidification increases this fraction to 90-99%. Addition of lactate with glutamine displaces part of the glutamine metabolized, but greatly stimulates the synthesis of alanine. Fatty acids depress ammonia production and blunt the tissue response to acidification. Gluconeogenesis from lactate is minimally influenced by incubation pH. It is concluded that the ATP turnover limits the metabolism of glutamine by proximal tubules in vitro as in vivo in the dog, and that the response to acidification is small in vitro because of the absence of alternative substrates.


Author(s):  
Gunter F. Thomas ◽  
M. David Hoggan

In 1968, Sugimura and Yanagawa described a small 25 nm virus like particle in association with the Matsuda strain of infectious canine hepatitis virus (ICHV). Domoto and Yanagawa showed that this particle was dependent on ICHV for its replication in primary dog kidney cell cultures (PDK) and was resistant to heating at 70°C for 10 min, and concluded that it was a canine adeno-associated virus (CAAV). Later studies by Onuma and Yanagawa compared CAAV with the known human serotypes (AAV 1, 2, 3) and AAV-4, known to be associated with African Green Monkeys. Using the complement fixation (CF) test, they found that CAAV was serologically related to AAV-3 and had wide distribution in the dog population of Japan.


Author(s):  
J. A. Nowell ◽  
J. Pangborn ◽  
W. S. Tyler

Leonardo da Vinci in the 16th century, used injection replica techniques to study internal surfaces of the cerebral ventricles. Developments in replicating media have made it possible for modern morphologists to examine injection replicas of lung and kidney with the scanning electron microscope (SEM). Deeply concave surfaces and interrelationships to tubular structures are difficult to examine with the SEM. Injection replicas convert concavities to convexities and tubes to rods, overcoming these difficulties.Batson's plastic was injected into the renal artery of a horse kidney. Latex was injected into the pulmonary artery and cementex in the trachea of a cat. Following polymerization the tissues were removed by digestion in concentrated HCl. Slices of dog kidney were aldehyde fixed by immersion. Rat lung was aldehyde fixed by perfusion via the trachea at 30 cm H2O. Pieces of tissue 10 x 10 x 2 mm were critical point dried using CO2. Selected areas of replicas and tissues were coated with silver and gold and examined with the SEM.


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