Glucocorticoid receptors in rat kidney cortical tubules enriched in proximal and distal segments

Mishina, Takao; Scholer, D; Edelman, Isidore S.

doi:10.1152/ajprenal.1981.240.1.f38

Cited by 18 publications

(12 citation statements)

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“…The concentration necessary to produce 50% of maximal stimulation (EC50) was < 1 nM. This value is in good agreement with generally recognized values for the K for dexamethasone binding to the glucocorticoid receptor ( 19,20). The glucocorticoid antagonist RU38486 (21) at a concentration of 1 ,uM produced no significant effect on the I.…”

Section: Resultssupporting

confidence: 85%

“…The dose response for the dexamethasone effect (Fig. 5) is close to that predicted from the kinetics of dexamethasone binding to the glucocorticoid receptor (19,20); the dexamethasone effect is blocked by the glucocorticoid receptor antagonist RU38486 (21) (Figs. 5 and 7); and, importantly, the dexamethasone effect is not inhibited by the mineralocorticoid receptor antagonist, spironolactone (Fig.…”

Section: Resultssupporting

confidence: 69%

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Enhancement of electrogenic Na+ transport across rat inner medullary collecting duct by glucocorticoid and by mineralocorticoid hormones.

Husted¹,

Laplace²,

Stokes³

1990

J. Clin. Invest.

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We have investigated the effect of steroid hormones on Na' transport by rat renal inner medullary collecting duct (IMCD) cells. These cells, grown on permeable supports in primary culture, grow to confluence and develop a transmonolayer voltage oriented such that the apical surface is negative with respect to the basal surface. The results of these experiments demonstrate that this voltage is predominantly (or exclusively) the result of electrogenic Na' absorption. Na' transport can be stimulated two-to fourfold by exposure to either dexamethasone or aldosterone (100 nM). Experiments using specific antagonists of the glucocorticoid and mineralocorticoid receptors indicate that activation of either receptor stimulates electrogenic Na' transport; electroneutral Na' transport is undetectable. Two other features of the IMCD emerge from these studies. (a) These cells appear to have the capacity to metabolize the naturally occurring glucocorticoid hormone corticosterone. (b) The capacity for K+ secretion is minimal and steroid hormones do not induce or stimulate conductive K+ secretion as they do in the cortical collecting duct. (J. Clin. Invest. 1990.

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Section: Resultssupporting

confidence: 85%

Section: Resultssupporting

confidence: 69%

Enhancement of electrogenic Na+ transport across rat inner medullary collecting duct by glucocorticoid and by mineralocorticoid hormones.

Husted¹,

Laplace²,

Stokes³

1990

J. Clin. Invest.

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“…Glucocorticoids increase endogenous acid production, stimulate acid secretion, enhance ammonium production, and induce phosphaturia (12)(13)(14). The site of action of glucocorticoids in decreasing phosphate reabsorption is largely confined to the proximal tubule (15), where glucocorticoid receptors have been found (16). In addition, we have recently reported that the glucocorticoid dexamethasone, but not the mineralocorticoid aldosterone, increases amiloride-sensitive Na+-H+ exchange activity and selectivity decreases Na+ gradient-dependent phosphate uptake in proximal tubule brush border membrane vesicles (17).…”

mentioning

confidence: 99%

Na+-H+ exchange activity in renal brush border membrane vesicles in response to metabolic acidosis: The role of glucocorticoids.

Kinsella¹,

Cujdik²,

Sacktor³

1984

Proc. Natl. Acad. Sci. U.S.A.

105

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Amiloride-sensitive Na+-H+ exchange activity in brush border membrane vesicles isolated from rat proximal tubule was increased in metabolic acidosis. The enhancement of exchange activity required an intact adrenal gland or glucocorticoid supplements. Ammonium and phosphate excretions were increased during acidosis and these were also largely dependent on an intact adrenal gland or glucocorticoid supplements. Amiloride-insensitive Na' uptake and passive H+ permeability were not altered by acidosis or the glucocorticoid status of the animal. These findings are consistent with glucocorticoids having an important regulatory role in the kidney by orchestrating the proximal tubular adaptation to metabolic acidosis.The kidney responds to metabolic acidosis by increasing secretion of acid, phosphate, and ammonium and by enhancing reabsorption of bicarbonate (1). Acid secretory processes provide a mechanism for bicarbonate reabsorption, 80%o of which occurs in the proximal tubule (2). This nephron segment is the locus of the Na+-H' exchanger (3). The carrier, found in the brush border membrane, mediates the electroneutral antiport of Na+ for H+ (4-6). Amiloride, at relatively high concentrations (Ki = 0.05 mM), competitively inhibits exchange activity (7).Metabolic acidosis is also associated with increased levels of adrenal corticosteroids (8-10). Adrenalectomy decreases renal net excretion of titratable acids and ammonium (8,9) and hyperglucocorticoid states are concomitant with metabolic alkalosis (11). Glucocorticoids increase endogenous acid production, stimulate acid secretion, enhance ammonium production, and induce phosphaturia (12)(13)(14). The site of action of glucocorticoids in decreasing phosphate reabsorption is largely confined to the proximal tubule (15), where glucocorticoid receptors have been found (16). In addition, we have recently reported that the glucocorticoid dexamethasone, but not the mineralocorticoid aldosterone, increases amiloride-sensitive Na+-H+ exchange activity and selectivity decreases Na+ gradient-dependent phosphate uptake in proximal tubule brush border membrane vesicles (17).These findings raise the possibilities that metabolic acidosis induces changes in renal brush border Na+-H+ exchange activity and phosphate and ammonium excretion and, further, that glucocorticoids may have a role in mediating these effects. The present communication addresses these questions.METHODS AND MATERIALS Animals: Dexamethasone Administration and Acid-Base Status. Male Sprague-Dawley rats weighing 200-320 g were fed Purina rat chow pellets ad libitum and had 0.9% saline in their drinking water for 6-8 days. Acidotic rats were given, in addition, 1% NH4Cl in the water. The adrenals of adrenalectomized animals were removed under light ether anesthesia on day 1. Dexamethasone-treated animals were given two injections (30 ,ug/100 g of body weight) of dexamethasone in 0.9% saline, 24 and 16 hr prior to sacrifice. The glucocorticoid dose approximated that reported to lead to a large increase in total...

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“…Glucocorticoids also induce phosphaturia (8,9). The site of action of glucocorticoids in decreasing Pi reabsorption is largely confined to the proximal tubule (10), where glucocorticoid receptors have been found (11).…”

mentioning

confidence: 99%

Glucocorticoids increase the Na+-H+ exchange and decrease the Na+ gradient-dependent phosphate-uptake systems in renal brush border membrane vesicles.

Freiberg¹,

Kinsella²,

Sacktor³

1982

Proc. Natl. Acad. Sci. U.S.A.

132

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The glucocorticoid dexamethasone, but not the mineralocorticoid aldosterone, increased amiloride-sensitive Na'-H' exchange activity in rat proximal tubule brush border vesicles. Na' uptake, independent of amiloride, was not affected. The glucocorticoid decreased the Na' gradient-dependent phosphate uptake. Uptake in the absence of a Na' gradient was not inhibited. Dexamethasone did not affect the Na' gradient-dependent D-glucose uptake. METHODS AND MATERIALS Animals and Steroid Administration. Male Sprague-Dawley rats (295-345 g) were fed Purina rat chow pellets ad lib. Rats were adrenalectomized under light ether anesthesia. After surgery, normal saline was given to prevent volume depletion. Adrenalectomized animals were divided into three groups. One group received twice daily subcutaneous injections of 0.3 ml of 0.9% saline. The other two groups received twice daily subcutaneous injections (5 pLg/100 g of body weight) of dexamethasone or aldosterone in 0.9% saline, respectively. The quantity of dexamethasone administered daily as the glucocorticoid replacement was approximately equivalent to the amount of corticosterone secreted per day by the rat and was the dose that effected a return of Na+, K+, and water movements in the rat colon to control values after adrenalectomy (18). Likewise, the quantity of aldosterone administered daily was approximately equivalent to the amount ofaldosterone secreted per day by rats on a normal diet (18). Another set of rats underwent only bilateral flank incisions, without removal of adrenals, and subsequently were given tap water to drink. This set ofanimals was subdivided into two groups. One group, designated sham, received twice daily subcutaneous injections of 0.3 ml of 0.9% saline. The other group, designated sham with dexamethasone, received dexamethasone (60 ,g/100 g of body weight) on the same schedule. Transport studies were performed 2 days after surgery. Hormones were last administered 2 hr prior to sacrifice. Animals were killed between 10:00 and 10:30 a.m.At the time ofsacrifice, serum Na+ concentration was slightly higher in adrenalectomized rats given aldosterone relative to the other groups, but the value was not statistically different from that found in adrenalectomized animals (141.6 ± 1.0 vs. 139.2 ± 0.5 milliequivalents/liter; P > 0.05). Serum Pi was essentially similar in all groups, varying from 2.66 ± 0.04 to 2.90 + 0.08 mM, although sham animals that received high doses of dexamethasone had-a Pi concentration that was minimally lower statistically than that in sham animals (2.70 ± 0.05 vs. 2.90 + 0.08 mM; P < 0.05), and adrenalectomized rats given maintenance doses of glucocorticoid had a slightly lower serum Pi concentration than did the adrenalectomized animal (2.66 ± 0.04 vs. 2.81 ± 0.06 mM; P < 0.05). Serum Ca2+ ranged from 2.35 ± 0.04 to 2.56 ± 0.04 mM. Sham rats given high doses of dexamethasone had the highest serum Ca2+ level. This was significantly greater (P < 0.05) than the values found in the other groups, which did not significan...

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Glucocorticoid receptors in rat kidney cortical tubules enriched in proximal and distal segments

Cited by 18 publications

References 0 publications

Enhancement of electrogenic Na+ transport across rat inner medullary collecting duct by glucocorticoid and by mineralocorticoid hormones.

Enhancement of electrogenic Na+ transport across rat inner medullary collecting duct by glucocorticoid and by mineralocorticoid hormones.

Na+-H+ exchange activity in renal brush border membrane vesicles in response to metabolic acidosis: The role of glucocorticoids.

Glucocorticoids increase the Na+-H+ exchange and decrease the Na+ gradient-dependent phosphate-uptake systems in renal brush border membrane vesicles.

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