Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Filtered glutathione (gamma-glutamyl-cysteinyl-glycine or GSH) is rapidly hydrolyzed by brush-border enzymes facing the tubular lumen and is reabsorbed in the form of the constituent amino acids. The first step of hydrolysis is catalyzed by gamma-glutamyltransferase (gamma-GT). We investigated localization and capacity of the rat renal glutathione degradation/reabsorption during elevation of the filtered load (intravenous infusion of 12 resp. 18 mumol GSH/min). Fractional excretion went up from about 0.003 to 0.31 +/- 0.02 SEM during infusion of the lower and to 0.49 +/- 0.03 SEM during infusion of the higher glutathione dose. GSH degradation/reabsorption took place along the entire proximal tubule and was partially saturated by a 150-200-fold elevation of the normal filtered load. Net reabsorption of GSH up to the last accessible superficial loop was significantly lower during infusion of 18 mumol GSH/min (0.3 mumol/min) than during infusion of 12 mumol GSH/min (1.6 mumol/min). In further experiments, infusion of 18 mumol GSH/min was preceded by the i.v. administration of acivicin (0.5 mmol/kg body wt.), an inhibitor of gamma-GT. In these experiments, fractional glutathione deliveries to late proximal and early distal tubules did not significantly differ from 1, fractional excretion of GSH at the same time was 1.46 +/- 0.11 SEM, revealing net secretion of GSH with the final urine. Tubular secretion of GSH in the acivicin-treated animals occurred either in distal tubules and/or collecting ducts or in the proximal tubules of deep nephrons which are not accessible to micropuncture.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Renal tubular transport of glutathione in rat kidney. 278 Feb 19

Since the reabsorption of lithium occurs almost exclusively in the proximal tubule and is associated with that of sodium, the fractional excretion of lithium (FELit) ws examined in 18 patients with cirrhosis in order to examine the reabsorption rate of sodium at the proximal tubule. As expected, the fractional excretion of sodium (FENa) was significantly lower in cirrhotic patients with ascites (0.43 +/- 0.10%, mean +/- SEM) than in cirrhotic patients without ascites (0.75 +/- 0.14%, P less than 0.05) and healthy controls (0.82 +/- 0.17%, P less than 0.05). By contrast, there was no significant difference in FELit among cirrhotic patients with ascites (16.7 +/- 2.0%), cirrhotic patients without ascites (15.4 +/- 2.0%) and controls (17.4 +/- 1.5%). It is unlikely, therefore, that in cirrhotic patients with ascites, the impaired sodium excretion is solely caused by the abnormal sodium reabsorption capacity of the proximal tubule.
 ...
PMID:A lithium clearance study of sodium reabsorption at the proximal tubule in liver cirrhosis with ascites. 280 32

Isolated kidney-cortical tubule suspensions and microdissected nephron segments from fed rats were used to study the action of catecholamines on gluconeogenesis. Gluconeogenesis from rat tubule suspension incubated with 5 mM pyruvate was stimulated maximally by 10(-5) M methoxamine, an alpha 1-selective agonist, and 10(-6) M noradrenaline by 29.2 +/- 5.2% (mean +/- SEM) and 32.6 +/- 2.9%, respectively. These effects were completely inhibited by 10(-7) M prazosin, a beta 1-selective antagonist. Yohimbine, an alpha 2-antagonist, also inhibited the effect, but only at a higher concentration (5 X 10(-5) M). Gluconeogenesis was not stimulated by isoproterenol, a alpha-agonist, at any concentrations between 10(-5) and 10(-7) M. With microdissected nephron segments, only the proximal tubule possessed gluconeogenic activity. Within the proximal tubule, the proximal convoluted tubule (PCT) revealed higher gluconeogenic activity than the proximal straight tubule (PST). Methoxamine at 10(-5) M stimulated gluconeogenesis in PCT, whereas in PST no increase of gluconeogenesis was observed. From these results, it can be concluded that an alpha 1-adrenergic agonist specifically stimulates renal gluconeogenesis in PCT, but not in PST.
 ...
PMID:Evidence that alpha-1-adrenergic stimuli specifically increase gluconeogenesis of the isolated proximal convoluted tubule in the rat. 287 97

gamma-Glutamyltransferase (gamma-GT) is located in the brushborder membrane of the proximal tubule where the catalytic site of the enzyme faces the lumen. The (phosphate-independent) glutaminase activity of gamma-GT in vitro is activated by hippurate. In order to investigate glutamine deamidation in the tubule lumen in vivo, 14C-L-glutamine-containing solutions were continuously microperfused through sections of the proximal convoluted tubule in vivo and in situ. D-aspartate and L-phenylalanine (10 mmol/l, each) were added to the perfusate in order keep the reabsorption of L-glutamine as such low and to block reabsorption of any glutamate possibly formed, respectively. Intraluminal formation of glutamate from glutamine in the absence of hippurate is small. In presence of 10 mmol/l hippurate, 5%-70% of the recovered 14C-activity was 14C-glutamate at an initial 14C-L-glutamine concentration of 1 mmol/l. The respective absolute rate (+/- SEM) of glutamate formation, i.e., 36 +/- 5 pmol X s-1 X m-1, was increased 1.4-fold at an initial L-glutamine concentration of 3 mmol/l, but dropped to one third at initially 0.3 mmol/l. A rough estimate of the apparent kinetic constants resulted in a Km of 0.58 (0.19-0.97) mmol/l and a Vmax of 56 (40-93) pmol X s-1 X m-1. Deamidation of glutamine occurred also in the absence of L-phenylalanine. Acivicin (AT 125), a gamma-GT inhibitor, completely blocked glutamate formation. Endogenous hippurate concentrations determined by free flow micropuncture and HPLC were 0.16 mmol/l in the late proximal convolution, 0.6 mmol/l in the early distal convolution, and 4.9 mmol/l in the final urine.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Ammoniagenesis catalyzed by hippurate-activated gamma-glutamyltransferase in the lumen of the proximal tubule. A microperfusion study in rat kidney in vivo. 288 Dec 49

1. Isolated kidneys taken from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were perfused over a range of perfusion pressures. 2. Lithium clearance was used as an index of proximal tubule sodium handling. 3. When the perfusate contained an oncotic agent (albumin, 6.7 g/dl) the SHR kidneys performed differently from the WKY kidneys with a reduction in inulin clearance, sodium excretion, fractional sodium excretion and fractional lithium excretion [at 105 mmHg (14 kPa) perfusion pressure, SHR 6.0 +/- 1.1% vs WKY 12.6 +/- 2.4% (mean +/- SEM); at 150 mmHg (20 kPa), SHR 17.1 +/- 1.6% vs WKY 27.0 +/- 2.3%]. Calculated indices of distal tubular function showed no major differences between SHR and WKY. 4. When kidneys were perfused without oncotic agent in the perfusate the differences between SHR and WKY in tubular handling of sodium and lithium were largely abolished. 5. These findings are consistent with the hypothesis that increased sodium reabsorption occurs in the proximal tubules of the kidneys of SHR and suggest that this is an intrinsic property of the kidney, not immediately dependent on neural or humoral factors. Increased sodium reabsorption in the proximal tubule may contribute significantly to the existence of hypertension in the SHR.
 ...
PMID:Sodium and lithium handling in the isolated hypertensive rat kidney. 292 26

Rubidium uptake into individual tubule cells of rat renal cortex as measured by energy-dispersive X-ray microanalysis on freeze dried cryosections was used as an index of potassium transport. Over a 30 second period following intravenous infusion of rubidium (0.5 mmol/kg body wt) rubidium content increased in all cells. After 30 seconds, rubidium contents were (in mmol/kg dry wt): 225 +/- 8 in distal convoluted tubule cells, 156 +/- 7 in connecting tubule cells, 110 +/- 7 in principal cells, 86 +/- 4 in proximal tubule cells and 24 +/- 2 in intercalated cells (mean +/- SEM). When distal sodium and potassium transport were stimulated by hypertonic saline loading, rubidium uptake was selectively increased into distal convoluted tubule cells by 38%, into connecting tubule cells by 36%, and into principal cells by 52%. However, rubidium uptake into proximal tubule and into intercalated cells remained unchanged. The preferential uptake of rubidium into distal convoluted tubule cells, connecting tubule cells, and principal cells correlates well with the known transport functions of sodium and potassium, whereas intercalated cells are distinguished by low sodium and potassium transport activity.
 ...
PMID:Cell rubidium uptake: a method for studying functional heterogeneity in the nephron. 336 55

The objective of this study has been to determine the intracellular localization of calcium in cryofixed, cryosectioned suspensions of kidney proximal tubules using quantitative electron probe X-ray microanalysis. Two populations of cells have been identified: 1) "Viable" cells, representing the majority of cells probed, are defined by their relatively normal K/Na concentration ratio of approximately 4:1. Their measured Ca content is 4.1 +/- 1.4 (SEM) mmol/kg dry wt in the cytoplasm and 3.1 +/- 1.1 mmol/kg dry wt in the mitochondria, or an average cell calcium content of approximately 3.8 mmol/kg dry wt. 2) "Nonviable" cells, defined by the presence of dense inclusions in their mitochondria and a K/Na concentration ratio of approximately 1. The Ca content is 15 +/- 2 mmol/kg dry wt in the cytoplasm and 685 +/- 139 mmol/kg dry wt in the mitochondria of such cells. Assuming 25 to 30% of the cell volume is mitochondrial, the overall calcium content of such nonviable cells is approximately 210 mmol/kg dry wt. The presence of these inclusions in 4 to 5% of the cells would account for the average total Ca content measured in perchloric acid extracts of isolated proximal tubule suspensions (approximately equal to 18 nmol/mg protein or 12.6 mmol/kg dry wt). Whole kidney tissues display a large variability in total Ca content (4.5 to 18 nmol/mg protein, or 3.4 to 13.5 mmol/kg dry wt), which could be accounted for by inclusions in 0 to 4% of the cells. The electron probe X-ray microanalysis (EPXMA) data conclusively demonstrate that the in situ mitochondrial Ca content of viable cells from the kidney proximal tubule is low and support the idea that mitochondrial Ca may regulate dehydrogenase activity but probably does not normally control cytosolic free Ca.
 ...
PMID:Heterogeneity of calcium compartmentation: electron probe analysis of renal tubules. 356 Feb

Urinary N-acetyl-beta-D-glucosaminidase (NAG), a proximal tubule lysosomal enzyme, has been used as an indicator of subtle renal injury. Since it has been positively and significantly correlated with hemoglobin A1c and microalbuminuria, it has been suggested that this enzyme may also reflect metabolic control. Albumin excretion is exacerbated in adult diabetic individuals during exercise; such exercise-induced albuminuria may be a forerunner of diabetic nephropathy. Metabolic control, degree of exertion, and duration of diabetes have been suggested to influence this increase in albuminuria during exercise. Studies of children are few and have produced inconsistent results. Thus we studied 28 insulin-dependent diabetic children ranging in age from 5 yr to 16 yr and 27 age-matched controls using treadmill exercise; two exercise periods consisting of (1) graded increases in speed and grade at 3-min intervals until exhaustion and (2) a constant speed and grade necessary to produce 2/3-3/4 maximal heart rate for 30 min were performed. Capillary blood glucose, urinary NAG/creatinine (cr) ratios (UNAG/Ucr) and urinary albumin/creatinine ratio (Ualb/Ucr) were measured before and after each exercise period; hemoglobin A1c was also measured. The latter averaged 11.8 +/- 0.6% (mean +/- SEM); contrary to previous studies, this was not correlated with pre- or postexercise UNAG/Ucr. During both exercise periods, blood glucose dropped 271 +/- 19 mg/dl to 213 +/- 21 mg/dl (period 1) and 230 +/- 22 mg/dl to 157 +/- 21 mg/dl (period 2).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of exercise on urinary N-acetyl-beta-D-glucosaminidase activity and albumin excretion in children with type I diabetes mellitus. 405 33

Maleate causes an enhanced excretion of amino acids, glucose, phosphate and bicarbonate. In addition to this inhibition of fluid and electrolyte reabsorption malate decreases glomerular filtration rate (GFR). The present investigation was designed to study the mechanisms of this fall in GFR. In group I (Sprague-Dawley rats; N = 8) maleate (2 mmol/kg body weight i.v.) increased the hydrostatic pressure in proximal tubule from 12.6 +/- 0.5 to 16.3 +/- 0.8 mm Hg (mean + SEM) and stop flow pressure in the first accessible loop of the proximal tubule was unchanged (33.6 +/- 0.4 vs 33.1 +/- 1.3 mm Hg; n.s.). Directly measured hydrostatic pressure in the glomerular capillaries in Munich-Wistar rats (N = 7), however, was reduced by maleate from 47.6 +/- 1.6 to 42.4 +/- 1.9 mm Hg. In group II (N = 8) we determined single nephron filtration rate (SNGFR) from distal and proximal collection sites in the same nephron in a paired fashion under control conditions and after maleate administration to assess the activity of the tubuloglomerular feedback. In the control periods SNGFR (16 nephrons) from distal collection sites was 26.3 +/- 1.6 nl/min whereas SNGFR from proximal collection sites was 31.8 +/- 2.4 nl/min. Following maleate distal SNGFR (17 nephrons) was 15.2 +/- 1.7 nl/min and proximal SNGFR was 24.3 +/- 2.2 nl/min. The ratio distal/proximal SNGFR was 1.23 +/- 0.07 under control conditions and increased to 1.76 +/- 0.1 following maleate indicating enhanced activity of tubuloglomerular feedback.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Maleate induced fall of glomerular filtration rate. A micropuncture study in the rat. 408 23

Prior studies of proximal tubule reabsorption have failed to distinguish conclusively between a separate active K+ transport system and K+ movement linked to Na+ reabsorption. To attempt to dissociate movement of K+ from Na+ and Ca++, recollection micropuncture experiments were performed in proximal tubules of intact and thyroparathyroidectomized (TPTX) dogs under two different conditions known to inhibit Na+ reabsorption: saline expansion to 5% body wt, and 5 mg/kg acetazolamide. A control hydropenic group was also studied. Tubular concentrations of K+, Na+, and Ca++ were measured by electron probe analysis. During initial collections, mean+/-SEM tubular fluid/plasma (TF/P)(K+) was 1.07 +/-0.05, 1.05+/-0.05, and 1.00+/-0.03 in intact hydropenic (n = 7), saline (n = 6), and acetazolamide (n = 8) groups; fractional reabsorption (FR) of K+ in proximal tubules was 0.35, 0.39, and 0.31 respectively. After saline, (TF/P)(Inul in) fell from 1.81 to 1.34 (P < 0.01); (TF/P)(K+), (TF/P)(Na+), and tubular fluid/ultrafiltrate, (TF/UF)(Ca++) did not change, so that FR of all three ions fell proportionately. After acetazolamide, however, despite a 24% inhibition of FR of Na+ and Ca++, (TF/P)(K+) fell to 0.85+/-0.04 (P < 0.005) so that FR of K+ was unchanged at 0.34. In three corresponding groups of TPTX dogs, similar results were obtained. Acetazolamide (n = 7) inhibited FR of Na+ and Ca++ by 41%, but (TF/P)(K+) fell from 1.03+/-0.03 to 0.89+/-0.04 (P < 0.005) so that FR of K+ was unchanged (0.36-0.34).A separate uphill transport system for K+ in proximal tubules is therefore unmasked by acetazolamide, a drug which selectively inhibits Na+ (and Ca++) reabsorption. Saline, on the other hand, inhibits net reabsorption of all three ions, probably by increasing passive backflux via intercellular channels.
 ...
PMID:Sodium-independent active potassium reabsorption in proximal tubule of the dog. 472 57


<< Previous 1 2 3 4 5 Next >>