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Biomedical subjects

S Klahr

Publications and source records attributed to S Klahr.

At least 199 records · Page 11Linked to original sources
PubMed1982

Decreased luminal membrane transport of phosphate in chronic renal failure.

To examine the effects of the hyperparathyroidism that accompanies chronic renal failure (CRF) on Pi transport across the renal proximal tubular luminal membrane, brush border membrane vesicles (BBMV) were prepared from the viable portion of the kidney of dogs with CRF or normal renal function. Initial rates of Na+ gradient-dependent Pi transport were decreased in BBMV from dogs with CRF compared with normal dogs. Initial rates of 22Na+ uptake in BBMV from dogs with CRF, however, were increased, suggesting a more rapid dissipation of the Na+ gradient in these vesicles. Initial rates of Pi transport measured under Na+-equilibrated conditions were decreased in BBMV from dogs with CRF. Parathyroidectomy of dogs with CRF abolished this decrease in Pi uptake. We conclude that the adaptations in Pi excretion associated with CRF are accompanied by changes in Na+-dependent Pi transport in BBMV and, therefore, possibly across the luminal membrane of the renal tubule. Moreover, the activity of this transport system can be altered by parathyroidectomy of dogs prior to isolation of BBMV.

Animals↗
PubMed1982

Uptake of Pi in brush border vesicles after release of unilateral ureteral obstruction.

After release of complete unilateral ureteral obstruction, a decreased fractional excretion of phosphate (Pi) is observed in the postobstructed kidney compared with the nonobstructed (control) kidney. To determine whether this decrease in the urinary excretion of Pi is due to changes in Na+-dependent Pi transport across the renal brush border membranes of postobstructed and control kidneys, membrane vesicles were prepared from the brush borders of kidneys from dogs that had undergone complete unilateral ureteral obstruction. Alkaline phosphatase activity was decreased in membrane vesicles isolated from postobstructed kidneys. No differences were observed in Na+-dependent Pi transport or in Na+ uptake in membrane vesicles isolated from postobstructed as compared with control kidneys. The in vivo administration of parathyroid hormone decreased Na+-dependent Pi transport in membrane vesicles isolated from postobstructed and control kidneys despite the absence of a phosphaturic response. Our findings suggest that no intrinsic change in the transport characteristics of Pi across the luminal membrane of renal tubular cells occurs with unilateral ureteral obstruction. The findings are consistent with the suggestion that the low fractional excretion of Pi in the postobstructed kidney results from very low filtered loads of Pi on the postobstructed side.

Animals↗
PubMed1982

Increased Na+-H+ exchange in brush border vesicles from dogs with renal failure.

In the remnant kidney model of chronic renal failure, absolute reabsorption of Na+ in the proximal tubule of the remaining nephrons is increased over normal. Absolute proximal tubular reabsorption of bicarbonate and proximal tubular H+ excretion per nephron have also been shown to be increased over normal in his model of renal disease. Na+ uptake in membrane vesicles isolated from the brush border membrane of remnant kidneys of dogs with chronic renal failure is increased over uptake in membrane vesicles isolated from kidneys of normal dogs. In the present studies an amiloride-sensitive, electroneutral Na+-H+ exchanger was identified in canine renal brush border membrane vesicles. Na+ uptake in membrane vesicles in the presence of an initial H+ gradient (intravesicular pH less than extravesicular pH) was increased in membrane vesicles isolated from the remnant kidneys of dogs with chronic renal failure over that in membrane vesicles from kidneys of normal dogs. This increase was abolished by amiloride. It is possible that the alterations in Na+ and bicarbonate reabsorption and H+ excretion in the remnant kidney model of chronic renal failure can be explained on the basis of increased activity of the Na+-H+ exchanger in the renal brush border membrane.

Animals↗
PubMed1982

Extraction of vitamin D metabolites by bones of normal adult dogs.

Using the isolated perfused canine tibia we examined the extraction of [(3)H]25(OH)D(3), [(3)H]1,25(OH)(2)D(3) and [(3)H]24,25(OH)(2)D(3) by bone of normal adult dogs. The studies were performed with and without vitamin D binding protein (DBP) in the perfusate to examine the effect of protein binding on the extraction of the vitamin D metabolites. An average of 48+/-2% of [(3)H]25(OH)D(3) was extracted by bone, when no DBP was present. However, addition of only a small amount of DBP ( approximately 720 ng/ml of perfusate) nearly completely abolished the extraction of [(3)H]25(OH)D(3) by bone. No degradation and/or transformation of the labeled 25(OH)D(3) could be demonstrated during passage through the isolated perfused bone. The extraction of [(3)H]24,25(OH)(2)D(3) in a DBP-free medium averaged 33+/-5%. Addition of 720 ng of DBP/ml of perfusate completely inhibited the extraction of this metabolite. The extraction of [(3)H]1,25(OH)(2)D(3) averaged 30+/-3% in a DBP free medium and no inhibition of the extraction was demonstrated after addition of DBP (720 ng/ml of perfusate). However, addition of DBP in a concentration of 14.4 mug/ml of perfusate reduced the extraction of 1,25(OH)(2)D(3) to 8+/-2%, a value still significantly higher than that seen after addition of 20 times less DBP to perfusions with 25(OH)D(3) and 24,25(OH)(2)D(3). It is concluded that the isolated perfused bone of normal dogs can extract significant amounts of 25(OH)D(3), 1,25(OH)(2)D(3), and 24,25(OH)(2)D(3). Small concentrations of DBP (720 ng/ml) in the perfusate significantly inhibited the extraction of 25(OH)D(3) and 24,25(OH)(2)D(3). A carrier role for DBP is suggested and it is proposed that the levels of free vitamin D are important for extraction of the metabolites by bone. Therefore, due to the different affinities of DBP for the various metabolites of vitamin D, only 1,25(OH)(2)D(3) is extracted in vitro in significant amounts by bone of normal adult dogs, in the presence of DBP.

Animals↗
PubMed1981

Studies on the role of the liver and splanchnic tissues in the production of carbohydrate intolerance in uremia.

The potential contribution of the splanchnic tissues to the carbohydrate intolerance of uremia was studied in fasted, partially nephrectomized rats. The livers of sham operated (C) and partially nephrectomized (Nx) rats were perfused with physiologic concentrations of potential gluconeogenic substrates using a nonrecirculating perfusion apparatus. Glucose release was slightly greater in the livers of Nx rats as compared to C rats. The portal vein concentrations of the potential gluconeogenic precursors were not different in the two groups. Moreover, there were no differences in the net hepatic extraction of alanine, glutamine or glutamate between the two groups of rats. There was also no difference in the production of glucose from U14C alanine. The livers of Nx rats, however, demonstrated less net extraction of lactate and released greater concentrations of betahydroxybutyrate. The increased release of glucose by livers of Nx rats may be at least partially due to their greater hepatic glycogen content.

Alanine↗
PubMed1981

Regulation of renal Na+-K+-ATPase in the rat by adrenal steroids.

The effects of single and multiple injections of aldosterone and dexamethasone on renal Na+-K+-ATPase, in vitro renal gluconeogenesis, and urinary electrolyte excretion were examined in adrenalectomized rats in a dose-dependent manner. Single maximal and supramaximal doses of aldosterone (defined by the effect of electrolyte excretion) had no effect on Na+-K+-ATPase or gluconeogenesis. By contrast, a single administration of dexamethasone (in a dose range that increased fasting blood sugar, stimulated renal gluconeogenesis, and had no mineralocorticoid effects) yielded clear-cut activation of Na+-K+-ATPase. Multiple submaximal doses of dexamethasone produced quantitatively similar stimulation of Na+-K+-ATPase and gluconeogenesis. Multiple supramaximal doses of aldosterone stimulated Na+-K+-ATPase and gluconeogenesis, but maximal and submaximal doses of the hormone were without effect. Aldosterone had no effect on hepatic Na+-K+-ATPase or gluconeogenesis. These results suggest that activation of renal Na+-K+-ATPase can be considered a putative glucocorticoid (not mineralocorticoid) effect. Renal Na+-K+-ATPase activation by chronic aldosterone treatment may be mediated by glucocorticoid receptor sites and, hence, may not represent a genuine mineralocorticoid effect.

Adrenal Cortex Hormones↗
PubMed1981

Altered adenylate cyclase kinetics in hyperfunctioning human parathyroid glands.

Current evidence suggests that parathyroid gland adenylate cyclase is involved in the control of parathyroid hormone (PTH) secretion. Thus, the altered control of PTH release in hyperparathyroidism may relate to altered adenylate cyclase activation. Therefore, we examined adenylate cyclase kinetics in membrane preparations from hyperfunctioning human parathyroid glands and normal human and bovine parathyroid tissues. There were no differences in the affinity for ATP between enzymes of normal and pathological tissue. However, the enzyme in 10 hyperfunctioning glands showed increased affinity for Mg++. The activation constant for Mg++ (KaMg) of adenylate cyclase in normal human glands was 10.6 +/- 2 mM, a value not different from that of normal bovine parathyroid tissue (9.5 +/- 1 mM). In contrast, the adenylate cyclase in membrane preparations from three of four hyperplastic and six of seven adenomatous human glands showed a markedly reduced KaMg, ranging from 0.85-1.64 mM and from 1.58-6.46 mM, respectively. In one adenoma and one hyperplastic gland, the Ka of the enzyme for Mg++ was close to normal. The addition of guanylylimidodiphosphate or GTP to the incubation mixture increased, in a dose-dependent manner, the apparent KaMg of the enzyme in the abnormal tissue toward normal, suggesting a defective nucleotide regulatory site in the adenylate cyclase of hyperparathyroid glands. In addition, the hyperparathyroid gland enzyme was less susceptible to inhibition by calcium, requiring 0.7-1 mM Ca++ for 50% inhibition, whereas comparable inhibition of the normal adenylate cyclase was seen at 0.22-0.28 mM Ca++. We conclude that the abnormal control of PTH secretion in hyperparathyroidism may be related, at least in part, to alterations in the characteristics of parathyroid gland adenylate cyclase.

Adenosine Triphosphate↗
PubMed1980

Production of thromboxane A2 by the kidney in glycerol-induced acute renal failure in the rabbit.

The hemodynamic alterations occuring in glycerol induced renal failure are controversial. To date no single humoral substance can fully explain the change in renal resistance observed in this hemodynamic model of acute renal failure. To assess the capacity of the rabbit kidney to produce thromboxane A2, a potent vasoconstrictor, the following experiments were carried out. Rabbits received 14 ml/kg of 50% glycerol subcutaneously 24 hrs before the study. After 24 hrs., the kidneys were removed and perfused ex vivo in superfusion bioassay cascade. Kidneys from rabbits which developed renal failure, as assessed by elevated serum creatinines, released a substance which produced contraction of rabbit aorta (RCS) in response to bradykinin (BK) and angiotensin II. Microsomes prepared from these kidneys when incubated with [14C]-arachidonic acid produced a peak of radioactivity which comigrated with thromboxane B2 on the thin layer chromatography and was inhibited by the thromboxane synthetase inhibitor imidazole. Furthermore, an inverse linear relation was found between the BK dose required to release RCS from perfused kidney and the serum creatinine levels. A direct linear relation was found between the percent of TxB2 produced by renal microsome preparations and the serum creatinine. These studies demonstrate an increased renal capacity of the glycerol-model of acute renal failure to produce TxA2. The production of TxA2 a potent vasoconstrictor should therefore be further evaluated as a potential endogenous mediator of the hemodynamic changes occurring in acute renal failure.

Acute Kidney Injury↗
PubMed1980

Isolation of epithelial cells from toad bladder.

The epithelial cells of the toad bladder have been isolated by brief exposure to ethylenediaminetetraacetic acid followed by treatment with collagenase, DNAse, and the application of shearing forces. This approach eliminates the need for scraping of the mucosal surface and reduces mechanical damage during harvesting of the epithelium. The method yields intact, isolated epithelial cells and few clumps. The three major types of epithelial cells described in the intact toad bladder were present in the final preparation. The cellular contents of nucleic acids and proteins (in pg/cell) were: DNA 22.5 +/- 1.1; RNA, 12.9 +/- 0.6; and protein, 192 +/- 9. The isolated cells possess rates of oxygen consumption and amino acid incorporation higher than those of epithelial sheets obtained by collagenase treatment and scraping of the intact bladder. However, the production of cyclic nucleotides in response to stimulation by vasopressin and carbachol is comparable in both preparations.

Amino Acids↗
PubMed1980

Mechanism of activation of renal Na+-K+-ATPase in the rat: effects of potassium loading.

The mechanism of activation of Na+-K+-ATPase after chronic potassium loading has been investigated in the rat kidney. Potassium loading stimulated the specific activity of Na+-K+-ATPase in the cortex and medulla of the kidney. This effect was not accompanied by a generalized increase in the cellular contents of RNA and proteins and could not be accounted for by an effect of potassium loading on renal growth. Enzyme induction does not appear to be mediated by changes in the endogenous levels of glucocorticoid or thyroid hormones. Evidence obtained from investigation of the partial reactions (Pi intermediate, ouabain-sensitive pNPPase) of the Na+-K+-ATPase enzymatic reaction is consistent with the interpretation that chronic potassium loading in the rat increases the number of enzyme units (Na+ pumps) in the cortex of the kidney. Analysis of the kinetic parameters (Km, K1/2, Vmax, Hill coefficients) of the enzymatic reaction indicates that K+ loading has little or no effect on the kinetic properties (affinity, cooperativity) of the stimulated transport enzyme.

Animals↗
PubMed1980

Mechanism of activation of renal Na+-K+-ATPase in the rat: effects of reduction of renal mass.

The mechanism of activation of renal Na+-K+-ATPase was studied in rats 2 wk after unilateral nephrectomy. The increase in enzyme specific activity was confined to the outer medulla and occurred without changes in the cellular contents of RNA or protein. Enzyme activation was accompanied by increases in the levels of the phosphorylated intermediate with little or no change in the apparent turnover numbers of the reaction. The specific activity of the ouabain-sensitive p-nitrophenylphosphatase also increased by uninephrectomy but to a larger extent than did Na+-K+-ATPase. Kinetic studies demonstrated an increase in Vmax for ATP, sodium, and potassium, and small increases in Km for ATP and K1/2 for potassium. There was no change in the activation energies or phase transition temperature to indicate alterations in the membrane environment of Na+-K+-ATPase. Adrenalectomy did not adversely affect activation. These results indicate that activation of renal Na+-K+-ATPase after reduction of renal mass occurs mainly by an increase in the number of sodium pump sites.

Adenosine Triphosphate↗
PubMed1980

Effects of parathyroid hormone on glucose production by the liver.

The present studies demonstrate a stimulatory effect of intact parathyroid hormone on hepatic glucose production in vivo. This increased glucose production was accompanied by augmented alanine uptake by the liver. In addition, PTH increased the conversion of 14C-alanine to 14C-glucose. These results suggest that the increased hepatic release of glucose produced by PTH is mediated in part by increased gluconeogenesis. On the other hand, the synthetic 1-34 amino terminal fragment of PTH, which is not extracted by the liver, did not stimulate hepatic glucose production.

Alanine↗