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S Klahr

Publications and source records attributed to S Klahr.

At least 181 records · Page 10Linked to original sources
PubMed1984

Na+ gradient-dependent Pi uptake in basolateral membrane vesicles from dog kidney.

To ascertain whether Na+ gradient-stimulated 32Pi uptake was demonstrable in renal basolateral membrane vesicles, we measured 32Pi uptake in basolateral membrane suspensions isolated from canine renal cortex and compared solute uptake in basolateral suspensions with that measured in brush border suspensions. Measurements revealed Na+ gradient-dependent 32Pi transport in basolateral preparations. D-[3H] Glucose uptakes in basolateral suspensions were not stimulated by the Na+ gradient in contrast to findings in brush border suspensions. Na+ gradient-dependent 32Pi transport in basolateral suspensions was electrogenic in contrast to that measured in brush border preparations. Unlike 32Pi uptake in brush border preparations, Na+ gradient-dependent 32Pi uptake in basolateral suspensions did not increase as extravesicular pH was increased from 6.5 to 7.5. Na+ gradient-dependent 32Pi uptake in basolateral membranes showed saturation over the range of [Pi] from 5 to 100 microM (apparent Km, 14 +/- 2 microM; apparent Vmax, 34 +/- 2 pmol Pi X mg protein-1 X 30s-1). Our findings are compatible with the presence of an electrogenic Na+-Pi cotransporter in the canine proximal tubular basolateral membrane.

Animals↗
PubMed1984

Glutamine transport in basolateral vesicles from dogs with acute respiratory acidosis.

It has been shown that acute respiratory acidosis in dogs results in enhanced renal extraction of L-glutamine from plasma and increased ammonia excretion per nephron. To determine whether a component of the enhanced L-glutamine extraction results from increased transport of L-glutamine across the basolateral membrane into the renal proximal tubular cell, we measured Na+ gradient-dependent L-[3H]glutamine transport in proximal tubular basolateral membrane vesicles isolated from kidneys of normal dogs and from kidneys of dogs following 2 h of acute respiratory acidosis. The initial rate of Na+ gradient-dependent L-[3H] glutamine uptake (15 s) was increased significantly in basolateral membrane vesicles from the acidotic compared with normal dogs. Increased uptake could be measured under conditions in which changes in membrane potential resulting from fluxes of solute were minimized. We conclude that an adaptation occurs in the basolateral membrane of the renal proximal tubular cell during acute respiratory acidosis that allows increased transport of L-glutamine across the membrane into the proximal tubular cell. This adaptation may permit increased ammonia production per nephron.

Acid-Base Equilibrium↗
PubMed1984

Uptake of Pi in basolateral vesicles after release of unilateral ureteral obstruction.

We previously demonstrated Na+-dependent 32Pi uptake in basolateral membrane vesicles from kidneys of normal dogs. We postulated that this reflects Na+-dependent Pi transport across the basolateral membrane into the proximal tubular cell in vivo that subserves cellular needs for Pi. To ascertain whether Pi transport across the basolateral membrane was enhanced in a condition in which delivery of Pi across the luminal membrane would be markedly decreased, we measured Na+-dependent 32Pi uptake in basolateral vesicles isolated from postobstructed and control kidneys of dogs following release of unilateral ureteral obstruction. Clearance of creatinine and filtered load of Pi were significantly decreased in postobstructed compared with control kidneys. Na+-dependent 32Pi uptake was increased in basolateral vesicles from postobstructed compared with control kidneys, as reflected by increased initial rate of uptake and an increased overshoot of 32Pi transport. Our findings are consistent with an adaptation resulting in increased transport of Pi across the basolateral membrane of the proximal tubular cell in unilateral ureteral obstruction. This process may provide required Pi to the cell under conditions in which decreased Pi is available for transport across the brush border membrane.

Animals↗
PubMed1984

Protein intake conditions the diuresis seen after relief of bilateral ureteral obstruction in the rat.

Natriuresis and diuresis occur in experimental animals after release of bilateral ureteral obstruction. Accumulation of urea and/or other natriuretic factors during the interval of complete obstruction may play a role in the ensuing postobstructive diuresis. The present experiments examine the potential role of dietary protein intake in conditioning the magnitude of the postobstructive diuresis after unilateral release of bilateral ureteral obstruction of 24-hr duration in the rat. Rats were fed isocaloric diets containing high (40% casein) or low (6% casein) protein for 4 weeks prior to obstruction. Rats fed a high protein diet had greater urine flows and fractional excretion of sodium and potassium after relief of obstruction than rats fed a low protein diet. Increased excretion of urea accounted for only part of the greater diuresis seen in rats fed a high protein diet. Hence, greater accumulation of other natriuretic factors during the period of obstruction in rats fed a high protein diet must play a role in the increased diuresis seen in this group of animals after release of obstruction.

Animals↗
PubMed1983

Lack of influence of 24,25-dihydroxyvitamin D3 on parathyroid hormone secretion from normal or hyperplastic glands.

The role of 24,25(OH)2D3 on parathyroid gland function remains controversial. The present studies were performed in vitro using (a) dispersed normal bovine parathyroid cells (bPTC) and (b) dispersed canine PTC (cPTC) prepared from glands of normal dogs, dogs with chronic renal failure (CRF), and dogs with CRF treated with 24,25(OH)2D3, 2.5 micrograms orally every day for more than 6 months. Bovine parathyroid cells were incubated for up to 180 min at 0.5, 1.0, and 3.0 mM external calcium in the presence or absence of 24,25(OH)2D3 (100 or 1000 nM). Similar experiments were conducted with cells incubated for 24 h in the presence of either the ethanol vehicle or 24,25(OH)2D3 (1000 nM). Parathyroid hormone secretion, measured in the supernatant by both C-terminal and N-terminal assays, did not show any differences between control and experimental groups at any time interval. Canine parathyroid cells obtained from uremic animals showed an average threefold increase in the total amount of PTH secreted, on a per cell basis over 180 min at 0.5 mM Ca2+, when compared with normal controls. However, there was no significant difference in PTH secretion at any level of calcium concentration between the cells obtained from parathyroid glands of CRF dogs and 24,25(OH)2D3-treated CRF dogs. Acute exposure to 24,25(OH)2D3 (1000 nM) in vitro of the cells obtained from the glands of CRF dogs also had no effect on PTH secretion. We conclude that 24,25(OH)2D3 has no direct effect on PTH secretion from dispersed parathyroid cells of either normal or uremic animals.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Effects of vitamin D metabolites on protein catabolism of muscle from uremic rats.

Epitrochlearis muscles obtained from normal male Sprague-Dawley rats used as controls (C) and rats with reduced renal mass (Nx) were incubated for 1 hr in Krebs-Ringer buffer containing 5 mM glucose with or without insulin, 25-hydroxycholecalciferol [25(OH)D3] or 1,25 dihydroxycholecalciferol [1,25(OH)2D3]. Plasma levels of 25(OH)D3 were unaffected by reduction in renal mass. Alanine (ALA), tyrosine (TYR), and phenylalanine (PHE) release rates from muscles of Nx rats were increased 40% above C values. Addition of 100 ng/ml of 25(OH)D3 to the incubating media reduced these release rates to C values within 1 hr of incubation. No additive effects with insulin were seen. Addition of 1 ng/ml of 1,25(OH)2D3 did not affect these results. Reduction of renal mass or the addition of insulin or 25(OH)D3 did not affect tissue concentrations of ATP or phosphocreatine. On the other hand, tissue levels of TYR and PHE were increased significantly (approximately equal to 20 to 25%) in muscles from Nx rats compared to C values and were reduced to control values by the addition of 25(OH)D3. The addition of insulin to the incubating media reduced the tissue levels of TYR and PHE in muscles of C rats by approximately equal to 20%, but reduced these levels in muscles of Nx rats by approximately equal to 55%. 25(OH)D3 did not affect tissue levels of cyclic AMP in muscles from either C or Nx rats. Protein synthetic rates were reduced significantly in muscles from Nx rats and returned to C values after 3 hr of incubation but were unaffected by 25(OH)D3. Muscle uptake of 3H,25(OH)D3 was reduced by approximately equal to 30% in muscles from Nx rats compared to C rats. These data suggest that increased muscle protein catabolism exists in rats with reduced renal mass which can be reduced to C values by 25(OH)D3 and does not appear to be mediated through stimulation of adenylate cyclase. 25(OH)D3 did not affect muscle protein synthetic rates. Reduced uptake of 3H,25(OH)D3 by muscles of Nx rats suggests that resistance to this vitamin metabolite may exist at the level of muscle in uremia.

Alanine↗
PubMed1983

Dissociation of membrane potential and hormone secretion in bovine parathyroid cells.

An increase in the calcium ion concentration of the medium from 0.5 to 2.0 mM is associated with a 65% decrease in the secretion of parathyroid hormone from dispersed parathyroid cells. This maneuver also depolarized the cell membrane from -55 to -21 mV as measured by the distribution of [3H]tetraphenylphosphonium ion between cells and medium. An increase in the potassium ion concentration of the medium to 50 mM caused a 67% increase in hormone secretion at 0.5 mM calcium and depolarized the cell to -31 mV. The high potassium did not significantly change hormone secretion or the membrane potential at 2.0 mM calcium. Chlorpromazine inhibited hormone secretion by 40% and depolarized the cell to -30 mV at 0.5 mM calcium in the medium. Chlorpromazine did not change hormone secretion or membrane potential in cells incubated at 2.0 mM calcium. These results suggest that depolarization of the cell by calcium cannot account by itself for the inhibition of hormone secretion and chlorpromazine mimics the effect of an increase in calcium on parathyroid cell function.

Animals↗
PubMed1983

Role of hexose monophosphate shunt in parathyroid hormone secretion.

The metabolism of labeled glucose by collagenase-dispersed bovine parathyroid cells was examined. When the medium calcium ion concentration was increased to 2.0 mM, the rate of 14CO2 release from [1-14C]glucose was increased 169 +/- 45% compared with the rate of 0.5 mM calcium. There was no significant change in the rate of 14CO2 release from [6-14C]glucose by this maneuver. The greatest increase in 14CO2 release and decrease in parathyroid hormone secretion occurred between medium calcium ion concentrations of 0.5-1.5 mM. This difference in the metabolism of glucose represents a true increase in hexose shunt activity because the incorporation of label from either [1-14C]- or [6-14C]glucose into parathyroid tissue lipids was equal. This suggests equilibration of label at the level of triose-phosphates. The increase in hexose shunt activity was not due to a calcium-mediated increase in glucose uptake because calcium changes did not affect 2-[3H]deoxyglucose transport by the cells. Phenazine methosulfate added to cells incubated at 0.5 mM calcium selectively increased hexose shunt activity in a dose-dependent manner (91 +/- 33% overall) and concomitantly inhibited parathyroid hormone secretion 65% overall at 0.5 mM calcium. The compound 6-aminonicotinamide inhibited hexose shunt activity but could not overcome the inhibition of hormone secretion at 2.0 mM calcium. A decrease in protein biosynthesis cannot fully explain the inhibition of hormone secretion by calcium or phenazine methosulfate because [3H]-leucine incorporation into total cell protein was not as affected as secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effects of prostacyclin on short-circuit current and water flow in the toad urinary bladder.

The effects of prostaglandins of the E series on sodium and water transport have been studied extensively. PGE2 has been shown to inhibit the increase in osmotic water flow produced by vasopressin and to stimulate short-circuit current (SCC) in the toad bladder. On the other hand, the effects of prostacyclin (PGI2), an arachidonic acid product, on sodium and water transport have not been extensively evaluated. The present studies describe the effects of PGI2 on basal and vasopressin-stimulated osmotic water flow and on SCC in the urinary bladder of the toad. Studies were performed in the absence or presence of indomethacin. PGI2 in the absence of indomethacin had no effect on basal or vasopressin-stimulated osmotic water flow. When indomethacin was present, thereby eliminating intrinsic prostaglandin biosynthesis, PGI2 inhibited basal but not vasopressin-stimulated osmotic water flow. PGI2 increased SCC in the presence or absence of indomethacin. 6-keto PGF1 alpha, the stable metabolite of PGI2, had no effect on SCC. PGI2 stimulated cAMP production in isolated toad bladder epithelial cells. 2',5'-Dideoxyadenosine, an inhibitor of cAMP production, blocked the increase in SCC produced by PGI2, suggesting that the effects of this compound on SCC are mediated via cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Metabolic acidosis and parathyroidectomy increase Na+-H+ exchange in brush border vesicles.

Na+-H+ exchange across the brush border membrane of the renal proximal tubular cell is a mechanism for Na+ reabsorption and H+ secretion. An electroneutral Na+-H+ exchange activity has been identified in isolated renal brush border membrane vesicles from rat and dog kidney, and increased Na+-H+ exchange has been measured in brush border membrane vesicles from remnant kidneys of dogs with chronic renal failure. To ascertain whether changes in H+ secretion by the kidney observed in chronic metabolic acidosis and in states of altered parathyroid function might result from altered Na+-H+ exchange across the renal cortical cellular brush border membrane, we measured Na+-H+ exchange in brush border membrane vesicles from kidneys of dogs with chronic metabolic acidosis and from kidneys of thyroparathyroidectomized dogs. Increased amiloride-sensitive Na+-H+ exchange was demonstrated in brush border membrane vesicles from kidneys of both groups of dogs, suggesting that adaptations in H+ excretion in chronic metabolic acidosis and hypoparathyroidism might be explained by increased activity of a renal brush border membrane Na+-H+ exchanger.

Acidosis↗
PubMed1983

Effect of unilateral ureteral obstruction on metabolism of renal lipids in the rat.

The metabolism of lipids in the cortex and inner medulla of control and experimental kidneys of rats with unilateral ureteral obstruction (UUO) was studied in vitro. A marked increase in the tissue triglyceride content was noted after 24 h of obstruction in the experimental kidney compared with the contralateral kidney of rats with UUO and normal kidneys from sham-operated rats. A decrease in total phospholipid content was seen in the experimental kidney after 24 h of obstruction. The incorporation of [1-14C]oleic acid or [14C]arachidonic acid into tissue triglycerides was significantly increased in the cortex and medulla of the experimental kidney of rats with UUO compared with either the contralateral kidney of the same animals or kidneys from sham-operated rats. The oxidation of [1-14C]oleic acid to 14CO2 and the incorporation of [14C]arachidonic acid into tissue phospholipids or free fatty acids were significantly lower in the experimental kidney of rats with UUO. The results strongly suggest an increase in the net synthetic rate of triglycerides in the experimental kidney of UUO rats. This increase may be related to both a decrease in fatty acid oxidation and an increased release of fatty acids from phospholipids presumably due to increased phospholipase activity.

Animals↗
PubMed1983

Altered adenosine 3',5'-monophosphate release in response to parathyroid hormone by isolated perfused bone from glucocorticoid-treated dogs.

The interaction between glucocorticoids (GC) and PTH has been suggested to play a role in the pathogenesis of GC-induced osteopenia. The present studies were designed to examine the effect of acute (5-h) or chronic (4-week) GC administration in vivo on 1) cAMP release by the isolated perfused dog tibia before (basal) and after the addition of synthetic bovine PTH-(1-34) [syn bPTH-(1-34)] (stimulated) to the perfusate in vitro, in the presence or absence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX; 1 mM), and 2) the percent arteriovenous difference of immunoreactive PTH across bone. Acute administration of 6 mg/kg methylprednisolone (MP) did not affect the basal release of cAMP from bone (6.9 +/- 1.6 pmol/min in control vs. 6.1 +/- 1.2 pmol/min in MP-treated animals); however, syn bPTH-(1-34) stimulated release of cAMP was higher in the MP-treated animals (45 +/- 8.1 pmol/min) than in controls (26.8 +/- 3.0 pmol/min). When IBMX was added to the perfusate, basal cAMP release was not different in control and MP-treated bone (17.2 +/- 2.1 pmol/min in control vs. 19.1 +/- 1.9 pmol/min in MP-treated bone), and syn bPTH-(1-34)-stimulated release of cAMP was equivalent in both groups. In contrast, chronic prednisone therapy lead to a decrease in both basal and PTH-stimulated release of cAMP from bone (3.1 +/- 0.4 and 6.9 +/- 1.6 pmol/min for basal, and 13.1 +/- 1.7 and 26.8 +/- 3.0 pmol/min for stimulated values, respectively). However, the percent changes from the basal levels were not different in the two groups. These results were correlated with histological studies of rib biopsies obtained from these animals, which showed evidence of osteopenia and decreased bone turnover. Neither acute nor chronic GC administration had any effect on arterio-venous differences for PTH across the bone. Thus, these studies demonstrate that 1) acute administration of MP enhances the response of bone to PTH, an effect that is not apparent in the presence of the phosphodiesterase inhibitor IBMX; and 2) chronic prednisone therapy decreased basal and PTH-stimulated cAMP release, an effect that correlated with histological evidence of decreased bone turnover.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Absence of metabolic bone disease in adult patients with the nephrotic syndrome and normal renal function.

Patients with the nephrotic syndrome and normal renal function have low levels of 25(OH)D in serum presumably due to the loss of this metabolite in the urine. Osteomalacia and hyperparathyroidism have been recently reported to occur as a consequence of those low levels of 25-hydroxyvitamin D (25OHD). We studied six patients (aged 26-52 yr) with the nephrotic syndrome (mean duration, 6.7 yr; range, 2-12 yr) and normal renal function, and evaluated their calcium, phosphorus, PTH, and vitamin D metabolite levels. Bone biopsies were obtained in all patients. The creatinine clearance ranged from 83-134 ml/min . 1.73 m2 of body surface, serum albumin was 2.65 +/- 0.42 (+/- SD) g/100 ml, and proteinuria ranged from 3.5-13.2 g/24 h. All patients had normal serum magnesium, phosphorus, ionized calcium, and alkaline phosphatase (total and bone fraction), and normal roentgenographic metabolic bone survey. Serum PTH, measured by the carboxy-terminal RIA, was 5.1 +/- 2.3 mu leq/ml (normal, 2-10), serum 250HD was 8.8 +/- 4.0 ng/ml (normal, 15-30), and 1,25-dihydroxyvitamin D3 was 38 +/- 25 pg/ml (normal, 17-58). Serum vitamin D-binding protein was 420 +/- 42 micrograms/ml (normal, 400-800). The histological appearance of bone biopsies obtained in these patients was not different from that in a group of sex- and age-matched controls. Specifically, there was no increase in the volume of osteoid (unmineralized bone), the percentage of trabecular surface covered by osteoid, or the number of osteoclasts. The cellular rate of mineralization was normal in all six patients. Thus, these data indicate that low serum levels of 250HD in patients with the nephrotic syndrome and normal renal function do not necessarily result in the development of osteomalacia and/or hyperparathyroidism.

Adult↗
PubMed1982

Inhibition by anticoagulant drugs of the progressive hypertension and uremia associated with renal infarction in rats.

We confirmed our previously reported findings that subcutaneous administration of heparin (200 U q 12 hr) in rats with experimental partial renal infarction prevents the development of progressive renal failure and hypertension, as well as the glomerular abnormalities which occur in the remaining viable renal tissue. In the present study, heparin, in the dosage used to prevent progressive renal failure, caused a marked and sustained prolongation of the activated partial thromboplastin time and prothrombin time, as well as a transient prolongation of the bleeding time. Administration of coumadin at doses which caused a significant prolongation of the prothrombin time and bleeding time also inhibited the development of progressive hypertension and uremia in rats with experimental partial renal infarction. These findings indicate that inhibition of blood coagulation effectively protects rats with experimentally decreased renal mass from the development of progressive renal failure and hypertension and support the concept that the glomerular thrombosis plays an important role in the pathogenesis of these complications.

Animals↗
PubMed1982

Abnormal skeletal response to parathyroid hormone in dogs with chronic uremia.

The release of cyclic AMP from bone in response to stimulation with PTH 1-34 was examined in 20 dogs with long-term chronic renal failure (CRF) produced by unilateral nephrectomy and contralateral partial renal artery ligation. After 9 to 15 months of uremia, the tibiae were removed and perfused in vitro. Seven dogs with CRF served as controls, 7 dogs with CRF were treated with 24,25(OH)2D3 - 2.5 micrograms per day, and 6 CRF dogs underwent thyroparathyroidectomy (TPTX) 42 h before they were sacrificed. The release of cyclic AMP from bone in response to PTH 1-34 in the CRF dogs was severely reduced compared to the response observed in 7 dogs with normal renal function (net accumulation of cyclic AMP release 86 +/- 8.5 versus 426 +/- 59.0 pmol/30 min). Long-term treatment of uremic dogs with 24,25(OH)2D3 had no effect on the release of cyclic AMP by bone. However, the release of cyclic AMP was restored to normal levels in the CRF dogs that underwent thyroparathyroidectomy. All CRF dogs had secondary hyperparathyroidism and the fact that TPTX returned the cyclic AMP response to normal values suggests that desensitization to PTH of the adenylate cyclase system of bone exists in chronic uremia.

24,25-Dihydroxyvitamin D 3↗