Effect of mineralocorticoid deficiency on ion and urea transporters and aquaporin water channels in the rat

Ohara, Miho; Cadnapaphornchai, Melissa A.; Summer, Sandra N.; Falk, Sandor; Yang, Jianhui; Togawa, Tatsuo; Schrier, Robert W.

doi:10.1016/s0006-291x(02)02634-7

Cited by 28 publications

(27 citation statements)

References 18 publications

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“…Ohara et al also showed that the mineralocorticoid-deficient rats that were given water had a significant increase in NKCC2/BSC1, but when the same rats were given normal saline in an effort to preserve intravascular volume, there was no change in NKCC2/BSC1 abundance (9). In the present study, all adrenalectomized rats received normal saline, so the lack of change in NKCC2/BSC1 that we observed is consistent with the results of Ohara et al (9) and suggests that the rats in the present study were not hypovolemic. Thus, it seems unlikely that hypovolemia contributed to the aldosterone-induced decrease in UT-A1 protein abundance in the present study.…”

Section: Discussionsupporting

confidence: 93%

“…Ohara et al (9) studied mineralocorticoid deficiency, induced by adrenalectomy with glucocorticoid replacement, and showed that it had no effect on UT-A1 protein abundance, regardless of whether the rats were given normal saline or plain water to drink. However, the presence of glucocorticoids may have altered any effect that would have resulted from mineralocorticoids alone.…”

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confidence: 99%

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Aldosterone Decreases UT-A1 Urea Transporter Expression via the Mineralocorticoid Receptor

Gertner¹,

Klein²,

Bailey³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Adrenalectomy in rats is associated with urinary concentrating and diluting defects. This study tested the effect of adrenal steroids on the UT-A1 urea transporter because it is involved in the urine-concentrating mechanism. Rats were adrenalectomized and given normal saline for 14 d, after which they received (1) vehicle, (2) aldosterone, or (3) spironolactone plus aldosterone. Adrenalectomy alone significantly increased UT-A1 protein in the inner medullary tip after 7 d, whereas aldosterone repletion reversed the effect. Spironolactone blocked the aldosterone-induced decrease in UT-A1, indicating that aldosterone was working via the mineralocorticoid receptor. For verifying that glucocorticoids downregulate UT-A1 protein through a different receptor, three groups of adrenalectomized rats were prepared: (1) vehicle, (2) adrenalectomy plus dexamethasone, and (3) adrenalectomy plus dexamethasone and spironolactone. Dexamethasone significantly reversed UT-A1 protein abundance increase in the inner medullary tip of adrenalectomized rats. When spironolactone was given with dexamethasone, it did not affect the dexamethasone-induced decrease in UT-A1. There was no significant change in serum vasopressin level, aquaporin 2, or Na ϩ -K ϩ -2Cl Ϫ co-transporter NKCC2/BSC1 protein abundances or UT-A1 mRNA abundance in any of the groups. In conclusion, either mineralocorticoids or glucocorticoids can downregulate UT-A1 protein. The decrease in UT-A1 does not require both steroid hormones, and each works through a different receptor.Adrenalectomy reduces urine-concentrating ability (1-3) but also inhibits acute water diuresis (4). Both glucocorticoids and mineralocorticoids must be administered to reverse the inhibition of acute water diuresis (4). Valtin and colleagues (4) showed that giving aldosterone to adrenalectomized rats after an acute water load corrected their diluting ability, whereas prednisolone corrected urine flow. These findings suggest that both adrenal steroids are involved in the regulation of urinary concentration and dilution.Urea plays an important role in the urine-concentrating mechanism (reviewed in (5)). We previously studied the effect of glucocorticoids (dexamethasone) on UT-A1 protein abundance in adrenalectomized rats. We showed that glucocorticoids decrease the protein abundance of the UT-A1 urea transporter in the inner medullary tip of adrenalectomized rats (6) and in conditions associated with excess glucocorticoid, such as uncontrolled diabetes (7,8). Presumably, in catabolic states in which glucocorticoid levels are increased, UT-A1 is downregulated to permit more nitrogenous waste to be excreted into the urine and to prevent excessive reabsorption of urea across the terminal inner medullary collecting duct (IMCD).The effect of mineralocorticoids (aldosterone) on UT-A1 protein abundance in adrenalectomized rats has not been studied. Ohara et al. (9) studied mineralocorticoid deficiency, induced by adrenalectomy with glucocorticoid replacement, and showed that it had no effect on ...

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Aldosterone Decreases UT-A1 Urea Transporter Expression via the Mineralocorticoid Receptor

Gertner¹,

Klein²,

Bailey³

et al. 2004

Journal of the American Society of Nephrology

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“…an increase in whole kidney AQP2 content, indicating a modulatory role of aldosterone on AVP-dependent AQP2 expression. In addition, Ohara et al (30) have recently shown that under the same conditions of aldosterone deficiency and hypovolemia, AQP2 expression levels are increased in the renal inner medulla. Because whole kidney AQP2 content is not, or at best, is slightly decreased in hypovolemic aldosterone-deprived rats, the increase in inner medullary AQP2 content implies a decrease in cortical and/or outer medullary AQP2 content.…”

Section: D)mentioning

confidence: 99%

Dual Influence of Aldosterone on AQP2 Expression in Cultured Renal Collecting Duct Principal Cells

Hasler

Mordasini

Bianchi

et al. 2003

Journal of Biological Chemistry

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In the renal collecting duct (CD) the major physiological role of aldosterone is to promote Na ؉ reabsorption. In addition, aldosterone may also influence CD water permeability elicited by vasopressin (AVP). We have previously shown that endogenous expression of the aquaporin-2 (AQP2) water channel in immortalized mouse cortical CD principal cells (mpkCCD C14 ) grown on filters is dramatically increased by administration of physiological concentrations of AVP. In the present study, we investigated the influence of aldosterone on AQP2 expression in mpkCCD C14 cells by RNase protection assay and Western blot analysis. Aldosterone reduced AQP2 mRNA and protein expression when administered together with AVP for short periods of time (<24 h). For longer periods of time, however, aldosterone increased AQP2 protein expression despite sustained low expression levels of AQP2 mRNA. Both events were dependent on mineralocorticoid receptor occupancy because they were both induced by a low concentration of aldosterone (10 ؊9 M) and were abolished by the mineralocorticoid receptor antagonist canrenoate. Inhibition of lysosomal AQP2 protein degradation increased AQP2 protein expression in AVP-treated cells, an effect that was potentiated by aldosterone. Finally, both aldosterone and actinomycin D delayed AQP2 protein decay following AVP washout, but in a non-cumulative manner. Taken together, our data suggest that aldosterone tightly modulates AQP2 protein expression in cultured mpkCCD C14 cells by increasing AQP2 protein turnover while maintaining low levels of AQP2 mRNA expression.Water permeability of the renal collecting duct (CD) 1 depends almost exclusively on the antidiuretic hormone [8-arginine]vasopressin (AVP), which exerts its action principally through tight regulation of aquaporin-2 (AQP2) expression. AQP2 belongs to the family of water channel proteins that facilitate osmotically driven water movement across cell membranes. At least six members of the AQP family (AQP1, AQP2, AQP3, AQP4, AQP6, and AQP7) are expressed in the kidney (1-4) and three of them, AQP2, AQP3, and AQP4, are expressed in CD principal cells (5-7). AVP increases CD water permeability by binding to the vasopressin V 2 -receptor located in the basolateral membrane of CD principal cells, an event that promotes AQP2 translocation from intracellular storage vesicles to the apical membrane (8). Water exits the cells through AQP3 and AQP4 water channels expressed in the basolateral membrane of CD cells. This process, induced by acute increases in AVP plasma concentration, occurs within minutes and is reversible. Declining levels of circulating AVP quickly lead to endocytotic retrieval of apical AQP2 and to reduced CD water permeability (8).Besides this rapid action, AVP also controls AQP2 expression over longer periods of time (from several hours to several days) (9). Accordingly, normal and AVP-deficient Brattleboro rats infused with AVP over a period of several days display increased levels of AQP2 expression (10, 13, 11). Conversely, animals admin...

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“…Sham operated animals received 100mg pellets of cholesterol. ADX animals were also given 0.5% saline to drink for the duration of the experiment to prevent alterations in sodium balance that result from loss of adrenal hormones [21]. After surgery, animals were given between 5-7 days recovery before beginning experimentation.…”

Section: Adrenalectomymentioning

confidence: 99%

Struggling behavior during restraint is regulated by stress experience

Grissom

Kerr

Bhatnagar

2008

Behavioural Brain Research

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Restraint elicits a number of physiological stress responses that can be increased or decreased in magnitude based on prior stress history. For instance, repeated exposure to restraint leads to habituation of hypothalamic-pituitary-adrenal (HPA) activation to restraint. In contrast, acute restraint after a different repeated stressor leads to facilitation of HPA activity to the novel stress. Acute restraint also elicits a variety of behaviors including struggling, but the effect of prior stress in regulating behavioral responses to restraint is not clear. The goal of the present studies was to assess struggling during restraint with or without a prior history of repeated stress. Using automated behavioral analysis software (EthoVision), we quantified struggling during restraint. We found that acutely restrained rats exhibit vigorous struggling behavior that declines during a single restraint period. Repeated restraint lead to habituated struggling behavior, whereas acute restraint after repeated swim elicited facilitated struggling behavior. These effects on struggling were found alongside expected differences in HPA activity. Removing stress-induced increases in corticosterone via adrenalectomy did not significantly affect struggling responses to restraint. Overall, restraintinduced struggling appears to be regulated in a manner similar to HPA responses to restraint, but is not dictated by adrenal hormones.

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Effect of mineralocorticoid deficiency on ion and urea transporters and aquaporin water channels in the rat

Cited by 28 publications

References 18 publications

Aldosterone Decreases UT-A1 Urea Transporter Expression via the Mineralocorticoid Receptor

Aldosterone Decreases UT-A1 Urea Transporter Expression via the Mineralocorticoid Receptor

Dual Influence of Aldosterone on AQP2 Expression in Cultured Renal Collecting Duct Principal Cells

Struggling behavior during restraint is regulated by stress experience

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