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Titolo:
Glucocorticoid-induced alterations of renal sulfate transport
Autore:
Sagawa, K; Darling, IM; Murer, H; Morris, ME;
Indirizzi:
SUNY Buffalo, Dept Pharmaceut, Amherst, NY 14260 USA SUNY Buffalo AmherstNY USA 14260 Dept Pharmaceut, Amherst, NY 14260 USA Univ Zurich, Inst Physiol, Zurich, Switzerland Univ Zurich Zurich Switzerland urich, Inst Physiol, Zurich, Switzerland
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 2, volume: 294, anno: 2000,
pagine: 658 - 663
SICI:
0022-3565(200008)294:2<658:GAORST>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
BORDER MEMBRANE-VESICLES; ALTERED DIETARY SULFATE; INORGANIC SULFATE; MESSENGER-RNA; RATS; REABSORPTION; COTRANSPORT; ADAPTATION; INHIBITION; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Morris, ME SUNY Buffalo, Dept Pharmaceut, 527 Hochstetter Hall, Amherst, NY 14260 USA SUNY Buffalo 527 Hochstetter Hall Amherst NY USA 14260 4260 USA
Citazione:
K. Sagawa et al., "Glucocorticoid-induced alterations of renal sulfate transport", J PHARM EXP, 294(2), 2000, pp. 658-663

Abstract

Glucocorticoid administration decreases renal sodium/phosphate cotransportin the proximal tubule due to a down-regulation of the sodium/phosphate cotransporter but has no effect on the sodium-dependent transport of glucose or proline. The objectives of the present investigation were to determine the effects of the glucocorticoid methylprednisolone (MPL) on 1) inorganic sulfate renal clearance in rats in vivo, 2) sodium/sulfate cotransport in kidney cortex membrane vesicles, and 3) the cellular mechanism of the MPL-induced alterations in sulfate renal transport. Male adrenalectomized Wistar rats received an i.v. dose of 50 mg/kg MPL or the vehicle. Urine samples were collected for 12 h after the administration of MPL, and blood samples were collected at the midpoint of the urine collection. Other animals were sacrificed at 4, 6, and 12 h after MPL administration, and the kidney cortex was removed for RNA or membrane preparations. Kidney cortex sodium/sulfate cotransporter (NaSi-1) mRNA levels were determined by reverse transcription-polymerase chain reaction and NaSi-1 protein levels were determined by enzyme-linked immunosorbent assay. The urinary excretion rate and renal clearance of sulfate were significantly increased in MPL-treated animals (144.0 +/- 27.0 versus 65.3 +/- 21.3 mu mol/12 h/kg and 0.208 +/- 0.038 versus 0.078+/- 0.025 ml/min/kg, mean +/- S.E., n = 9-12 in treated versus control). The V-max value for sodium-dependent sulfate transport in brush border membrane vesicles (representing reabsorption in the proximal tubules) was significantly decreased in MPL-treated animals compared with controls (0.68 +/- 0.07 versus 0.88 +/- 0.05 nmol/mg of protein/10 s, mean +/- S.E.). There wasno change in the K-m value for sodium/sulfate cotransport in brush-border membrane and no change in sulfate/anion exchange in basolateral membrane vesicles. Membrane fluidity in brush border membrane and basolateral membranevesicles, determined by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene was unaltered by MPL treatment. NaSi-1 mRNA levels were significantly decreased at 4 and 6 h, but not 12 h, after MPL administration, whereas NaSi-1 protein expression was significantly decreased at 4, 6, and 12 h. Therefore, MPL treatment increases the renal clearance of inorganic sulfate, at least in part, due to down-regulation of NaSi-1 mRNA and protein expression in the kidney.

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Documento generato il 12/07/20 alle ore 06:26:45