Rat Renal Slices Research Articles

Prostaglandin biosynthesis does not participate in isoproterenol-induced renin release

Rat renal slices were incubated in two different media. One was a normal K. physiological saline solution and the other a high K medium. Renin release was measured every 15 min in the presence and absence of 10 −6M isoproterenol and also in the presence and absence of aspirin, 0.8 or 1.6 ×10 −5M. In all experiments renin release was linear during the 75 min of incubation. Isoproterenol increased renin release by approximately 100%. This was the case even in the presence of aspirin which significantly inhibited prostaglandin release (PGE 2, PGF 2 α and 6-keto-PGF 1 α). Nor was there any reduction in the basal secretory rate by aspirin alone. These data are taken to indicate that aspirin in pharmacological doses does not interfere with either in vitro basal release rates of renin, nor the response to B agonists. It is also suggested that B agonists do not exert their effect by stimulating prostaglandin secretion.

The regulation of renal ammoniagenesis in the rat by extracellular factors. III. Effects of various fuels on in vitro ammoniagenesis

The addition of many oxidizable substrates to the medium of incubating rat renal slices decreases ammoniagenesis from glutamine and glutamate. Interestingly, lactate and β-hydroxybutyrate depress ammoniagenesis less in renal slices from acidotic rats compared with normal-control rats. In this study, the effects of an expanded panel of substrates on ammoniagenesis in kidney slices from control and acidotic rats were followed to discern patterns of inhibition. In addition to lactate and β-hydroxybutyrate, acetate, pyruvate, and perhaps acetoacetate caused relatively less depression of ammoniagenesis in acidotic slices. Citrate, succinate, fumarate, octanoate, and α-ketoglutarate decreased ammoniagenesis to the same extent or more in acidotic slices compared with that in normal-control slices. Glycerol had little effect on ammoniagenesis under either condition. From the substrates tested, it can be generalized that those outside the TCA cycle (with exception of octanoate) depress ammoniagenesis less during acidosis, while those in the TCA cycle depress ammoniagenesis equally or even more during acidosis. We hypothesize from the pattern of our results that changes in renal intermediary metabolism at or before citrate formation occur during acidosis and are important regulatory mechanisms for ammoniagenesis.

Effect of Cinoxacin on ceLlular metabolism in rat kidney cortical slices

Cinoxacin (CINX) is known to be secreted by renal tubules and to cause renal damage at very high doses only in rats. In order to know the mode of CINX transport and its effect on cellular metabolism in the kidney, effects of CINX on p-aminohippurate (PAH) transport and cellular function were examined using renal cortical slices of rat and rabbit as compared with nalidixic acid (NA) with no nephrotoxic action. CINX competitively inhibited PAH accumulation in rat renal slices without affecting the Na gradient across cell membranes. Incubating the slices with CINX caused an accumulation of CINX which was inhibited by PAH. Effects of+CINX mM) on water content, inulin space, transports of Na+ and K, ATP content and oxygen consumption of the slices werç not detected in rat renal slices, but CINX suppressed the Na transport in rabbit kidney slices. On the other hand, NA (5 mM) depressed all parameters mentioned above in rat and water content and Na transport in rabbit. CINX and NA had no effect on the release of N-acetyl-β-D-glucosaminidase from renal slices of rat and rabbit. These results suggest that CINX is transported by the same process as PAH and has no effect on cellular function. So, the renal damage caused by CINX in rat appears to be due to physical trauma resulting from deposition of CINX crystals in the urinary tract.

Mechanisms of Organic Acid and Monosaccharide Transport in the Kidney of the Brush-tailed Possum, Trichosurus vulpecula

The mechanisms of organic acid and monosaccharide transport in the kidney of T. vulpecula were investigated using the renal cortical slice preparation. The kinetics, the sensitivity to inhibitors of metabolism and sodium transport, and the specificity of the concentrative uptake of p-amino-hippurate and alpha-methyl-D-glucoside were examined and compared with published results from studies in eutherian mammals. Some minor differences between metatherians and eutherians were noted with regard to the specificities of the renal slice uptake systems. Penicillin G, a competitor of organic acid transport in eutherian kidneys, did not interact with the marsupial uptake system, and sodium acetate, which stimulates transport in other mammals, inhibited p-aminohippurate uptake in the slice of the possum kidney. 2-Deoxy-D-glucose, which interacts with the phlorizin-sensitive monosaccharide transport system in the dog, rat and rabbit kidney, had no effect on alpha-methyl-D-glucoside uptake in the possum, and the magnitude of the interaction of D-fructose resembled that reported in the dog and rat but was greater than the inhibition reported in the rabbit. D-Glucuronic acid and D-glucuronic acid lactone inhibited alpha-methyl-D-glucoside uptake in the possum but had no effect on uptake in rat renal slices. In consideration of the reported variability of these parameters between different classes of eutherians, it was concluded that the primary mechanisms involved in organic solute transport by the proximal nephron of metatherians and eutherians were not significantly different.

The regulation of renal ammoniagenesis in the rat by extracellular factors. II. Ammoniagenesis by rat kidney slices incubating in normal acidotic sera

Kidney slices from normal rats incubating in 100% v/v rat serum produce less ammonia than slices incubating in medium containing comparable amounts of glutamine. When lactate in concentration, expected in serum, is added to medium containing glutamine, ammoniagenesis by rat renal slices is similar in magnitude to ammoniagenesis by rat renal slices incubating in serum. In contrast, ammonia production by slices from acidotic rats is near similar whether incubation takes place in glutamine, glutamine plus lactate, or in serum (100% v/v). The source of the serum used for incubation does not matter. For the most part, ammonia production by renal slices from the same rats (control or acidotic) was indistinguishable whether the serum came from a control or acidotic rat. Based upon the similarity between findings with serum and with medium containing lactate, we feel that lactate and other oxidizable substrates in serum decrease glutamine ammoniagenesis. This hypothesis was strengthened when it was shown that ultrafiltrates of sera act similarly to whole sera, while dialysis of sera, to a great extent, removes many of the inhibitors. We further conclude that circulating oxidizable substrates in sera have less effect on renal ammoniagenesis by acidotic slices, and this relative insensitivity to the circulating depressors could be important in adaptive ammoniagenesis.

Effects of acid challenge on in vivo and in vitro rat renal ammoniagenesis

This study compares the ability of different strengths of NH 4Cl, CaCl 2, and HCl to affect the termporal excretion of ammonium in rats. Oral NH 4Cl given in a single dose of 0.5 mmole, 1.0 mmole and 1.5 mmole/100 g BW steadily increases ammonium excretion in rats. The majority of the augmented ammonium excretion is secondary to increased renal production — not to changes in urine pH or urine volume. Acute challenges greater than 1.5 mmole/100 g BW do not increase ammonium excretion further. Results were similar when chronic acid challenge was investigated — greater NH 4Cl challenges cause greater ammonium excretion. Challenges beyond 1.5 mmole/100 g BW bid frequently cause death unless the rats are preconditioned (made mildly acidotic) prior to initiation of this dose. At the 1.5 mmole/100 g BW dose, maximal ammonium excretion is reached by day 2 or 3. Thus, maximal renal ammoniagenesis during acid stress occurs rapidly, and at different times depending on the strength of the acid challenge. CaCl 2 or HCl offer no advantages over NH 4Cl as acidifying agents. In addition to the above, there is a significant correlation between ammonium excretion in vivo and the ability of rat renal slices to produce ammonia from glutamine or glutamate in vitro .

Inhibition of gluconeogenesis in rat renal cortex slices by metabolites of L-tryptophan in vitro.

The inhibitory effects of metabolites of L-tryptophan on gluconeo-genesis in rat renal cortex has been established. 1. Glucose production was inhibitied by quinolinate in vitro. The inhibition is due to the decreased phosphoenolpyruvate carboxykinase activity. As suggested for purified enzyme systems, quinolinate seems to exert its action in tissue slices by chelating divalent metal ions. The minimum effective extracellular concentration of the inhibitor was 5 X 10(-5) M with pyruvate as a precursor for gluconeo-genesis. 2. The effect of 3-hydroxyanthranilate is stronger (minimal effective concentration 10(-5) M) than that of quinolinate. 3-Hydroxyanthranilate may be effective in its original form and/or as a dimer degrandation product. The compound(s) exert a second effect in addition to blocking the phosphoenolpyruvate carboxykinase. This block is attained by conversion of 3-hydroxyanthranilate to quinolinate. The non-quinolinate mediated effect may be due to a reduced ATP regeneration. 3. It is suggested that kidney cortex responds sensitively to disturbances in ATP metabolism by reduction of glucose synthesis, when it is not the result of blocked formation of phosphoenolpyruvate.

Ammonia production from glutamine and glutamate in isolated dog renal tubules.

ARTICLESAmmonia production from glutamine and glutamate in isolated dog renal tubulesHG PreussHG PreussPublished Online:01 Jan 1971https://doi.org/10.1152/ajplegacy.1971.220.1.54MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByRenal Ammonia Production and Excretion1 January 2011Hormonal Control of Renal Ammonium Metabolism: A ReviewAmerican Journal of Kidney Diseases, Vol. 14, No. 4Acidotic alterations in oxidative metabolism influencing rat renal slice amnoniagenesisLife Sciences, Vol. 41, No. 14Ammonia production and amino acid metabolism by rat renal papillary epithelial cells in culture.Journal of Biological Chemistry, Vol. 260, No. 1The regulation of renal ammoniagenesis in the rat by extracellular factors. III. Effects of various fuels on in vitro ammoniagenesisMetabolism, Vol. 32, No. 9Influence of pyruvate on ammonia metabolism by renal cortical mitochondriaKidney International, Vol. 22, No. 3The kidney of chicken adapts to chronic metabolic acidosis: In vivo and in vitro studiesKidney International, Vol. 22, No. 2Effects of in vitro potassium on ammoniagenesis in rat and canine kidney tissueKidney International, Vol. 21, No. 2Evidence for activation of the renal glutamate dehydrogenase pathway in intact acidotic dogsKidney International, Vol. 19, No. 4Regulation of renal ammoniagenesis during acidosis: The pyridine nucleotide hypothesis revisitedLife Sciences, Vol. 27, No. 24RESPONSE OF THE RAT AND DOG KIDNEY TO H+ CONCENTRATION IN VITRO—A COMPARATIVE STUDY WITH SLICES AND TUBULESEFFECT OF pH ON METABOLISM OF THE GLUTAMINE CARBON SKELETON BY RENAL CORTICAL MITOCHONDRIAEffects of fluorocitrate on renal ammoniagenesis and glutamine metabolism in the intact dog kidneyKidney International, Vol. 15, No. 3Lactate and pyruvate metabolism in isolated renal tubules of normal dogsKidney International, Vol. 14, No. 6The regulation of renal ammoniagenesis in the rat by extracellular factors. I. The combined effects of acidosis and physiologic fuelsMetabolism, Vol. 27, No. 11Gluconeogenesis and ammoniagenesis in rat kidney: Effect of 3-mercaptopicolinic acid19 October 2001 | FEBS Letters, Vol. 65, No. 2Renal Metabolic Processes and Acid-Base ChangesMedical Clinics of North America, Vol. 59, No. 3Role of ammonia as a buffer in the central nervous systemRespiration Physiology, Vol. 22, No. 3 More from this issue > Volume 220Issue 1January 1971Pages 54-58 Copyright & PermissionsCopyright © 1971 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1971.220.1.54PubMed5538672History Published online 1 January 1971 Published in print 1 January 1971 Metrics

Dothiosulfate and sulfate utilize the same renal transport process?

Several workers have discussed the possibility that SO 4 2− and S 2O 3 2− the same renal transport mechanism. For example in Lophius americanus Berglund and Forster 1 concluded that there existed a single secretory system for the divalent anions, SO 4 2− and S 2O 3 2−. Berglund et al. 2 have proposed a similar interaction for the reabsorptive process. The present work was undertaken to examine whether or not the correspondence suggested by the in vivo studies was substantiated by in vitro studies. Several parameters were examined for both SO 4 2− and S 2O 3 2− accumulation by rat renal slices and in most circumstances good agreement was not noted. For example, although the differences noted between rat and rabbit tissue were the same for both anions, and the estimated initial rates of uptake for SO 4 2− and S 2O 3 2− were approximately the same, other similarities were less obvious. The apparent K m values for the two uptake processes were different. The patterns of response to phlorizin in the presence of and absence of glucose were different for S 2O 3 2− than those reported in the literature for SO 4 2−. Differences were also noted in the S 2O 3 2− uptake at different temperatures compared to literature reports for SO 4 2−. Also S 2O 3 2− uptake was greater in the absence of Na + than was SO 4 2− uptake. Finally, no effects of amino acids were noted on S 2O 3 2− accumulation, while certain amino acids reduced SO 4 2− uptake.

Failure of cirrhotic sera to inhibit renal tubule hippurate transport in vitro.

SummaryIn order to evaluate possible depression of renal hippurate transport by cirrhotic sera, hippurate transport into rat kidney slices incubated in sera from cirrhotic and normal patients was investigated. Unlike studies with uremic sera, there was no significant difference in hippurate uptake in rat renal slices incubated with cirrhotic sera when compared to normal sera. It is suggested by this in vitro technique that a metabolic inhibitor of hippurate transport is not present in cirrhotic sera and that other factors, such as renal tubule function per se or changes in renal hemodynamics, may contribute to the decreased PAH uptake observed in vivo in the cirrhotic patient.

Effects of adrenalectomy, aldosterone and dehydration on electrolyte metabolism of rat renal cortex slices.

An attempt has been made to study the action of aldosterone on tubular reabsorption of sodium using in vitro incubation of rat renal cortex slices. In normally hydrated animals neither adrenalectomy nor aldosterone, whether injected into the animal or added to the incubation medium, influenced significantly the rate and extent of slice sodium and water accumulation and potassium depletion. However, effects on other variables were found. After adrenalectomy, the oxygen consumption of the renal cortical tissue was decreased 10–13.5% and the ammonia production 27–33%. Unlike oxygen consumption, ammonia production was influenced by aldosterone; when the hormone was injected into rats the renal cortical ammonia production increased 27–65%. Ammonia concentrations in the incubation media could account for the progressive alkalinization observed with increasing time of incubation. Hydropenia resulted in an increased sodium accumulation and potassium depletion, and a decreased oxygen consumption and ammonia production by incubated slices from intact as well as adrenalectomized rats.