Reversible downregulation of thiazide diuretic receptors by acute renal ischemia

Beaumont, Kevin; Vaughn, Duke A.; Maciejewski, Andrzej R.; Fanestil, Darrell D.

doi:10.1152/ajprenal.1989.256.2.f329

Cited by 10 publications

(7 citation statements)

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“…Thiazide receptor density is rapidly and reversibly down-regulated by renal ischemia of short duration (10 minutes), suggesting the presence of active intracellular regulatory mechanisms such as phosphorylatioddephosphorylation (28). The results of the present study, in which thiazide receptor density was significantly lower in male than in female rats, indicate that thiazide receptors may be hormonally-regulated.…”

Section: T H I a Z I D E D I U R E T I C Receptors I N Hypertensive Ratssupporting

confidence: 42%

Thiazide Diuretic Receptors in Spontaneously Hypertensive Rats and 2-Kidney 1-Clip Hypertensive Rats

Beaumont

Vaughn

Casto

et al. 1990

Clinical and Experimental Hypertension. Part A: Theory and Prac

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Thiazide diuretic receptor density was assessed in kidneys from spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats by measuring hydroflumethiazide-displaceable 3H-metolazone binding to renal membranes in vitro. Renal thiazide receptor density was not significantly different in 4 week old SHR and WKY rats, but was significantly increased by 20%-40% in 14-49 week old SHRs compared to WKY rats. Affinity of receptors for 3H-metolazone did not differ between SHRs and WKY rats at any age. In WKY rats with 2 kidney-1 clip (2K-1C) hypertension, thiazide receptor density was not significantly different in either clipped or unclipped kidneys from sham-operated controls. Thus, increased renal thiazide receptor density occurs in SHRs along with the development of hypertension and does not appear to be secondary to increased renal perfusion pressure. This increase may reflect altered hormonal or ionic input to the distal tubule and may contribute to elevated sodium reabsorption in this segment in the SHR.

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Section: T H I a Z I D E D I U R E T I C Receptors I N Hypertensive Ratssupporting

confidence: 42%

Thiazide Diuretic Receptors in Spontaneously Hypertensive Rats and 2-Kidney 1-Clip Hypertensive Rats

Beaumont

Vaughn

Casto

et al. 1990

Clinical and Experimental Hypertension. Part A: Theory and Prac

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“…Recently, a tilapia ortholog of zNCC-like 2, tNCC-like, was reported to be expressed in apical membranes of the tilapia skin/gill epithelia with a specific homologous antibody (17,21,29). In the Xenopus oocytes that overexpressed rat and winter flounder NCCs, the inhibitory effect of metolazone (an NCC-specific inhibitor) was examined in terms of Na ϩ influx (2). In the present in vivo study, metolazone was found to inhibit both Na ϩ and Cl Ϫ influxes in 5-dpf zebrafish embryos, the skin ionocytes of which express zncc-like 2.…”

Section: Discussionmentioning

confidence: 99%

Role of SLC12A10.2, a Na-Cl cotransporter-like protein, in a Cl uptake mechanism in zebrafish (Danio rerio)

Wang

Tseng

Yan

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

126

170

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The thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), a member of the SLC12 family, is mainly expressed in the apical membrane of the mammalian distal convoluted tubule (DCT) cells, is responsible for cotransporting Na(+) and Cl(-) from the lumen into DCT cells and plays a major role in the mammalian renal NaCl reabsorption. The NCC has also been reported in fish, but the functional role in fish ion regulation is yet unclear. The present study used zebrafish as an in vivo model to test the hypothesis of whether the NCC plays a role in Na(+) and/or Cl(-) uptake mechanisms. Four NCCs were cloned, and only one of them, zebrafish (z) slc12a10.2 was found to predominately and specifically be expressed in gills. Double in situ hybridization/immunocytochemistry in zebrafish skin/gills demonstrated that the specific expression of zslc12a10.2 mRNA in a novel group of ionocytes differed from those of the previously-reported H(+)-ATPase-rich (HR) cells and Na(+)-K(+)-ATPase-rich (NaR) cells. Gill mRNA expression of zslc12a10.2 was induced by a low-Cl environment that stimulated fish Cl(-) influx, while a low-Na environment suppressed this expression. Incubation with metolazone, a specific inhibitor of the NCC, impaired both Na(+) and Cl(-) influx in 5-day postfertilization (dpf) zebrafish embryos. Translational knockdown of zslc12a10.2 with a specific morpholino caused significant decreases in both Cl(-) influx and Cl(-) content of 5-dpf zebrafish embryos, suggesting that the operation of zNCC-like 2 results in a net uptake of Cl(-) in zebrafish. On the contrary, zslc12a10.2 morphants showed increased Na(+) influx and content that resulted from upregulation of mRNA expressions of Na(+)-H(+) exchanger 3b and carbonic anhydrase 15a in HR cells. These results for the first time provide in vivo molecular physiological evidence for the possible role of the NCC in the Cl(-) uptake mechanism in zebrafish skin/gills.

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“…E) ISCHEMIA. Beaumont et al (12) noted that warm ischemia reduced the number of [ 3 H]metolazone binding sites in rat kidney cortex. As little as 10 min of warm ischemia was sufficient to reduce the number of receptors significantly, and 30 min reduced them close to background.…”

Section: Regulation Of Na ϩ and CL ϫ Transportmentioning

confidence: 99%

Mammalian Distal Tubule: Physiology, Pathophysiology, and Molecular Anatomy

Reilly¹,

Ellison²

2000

Physiological Reviews

317

283

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The distal tubule of the mammalian kidney, defined as the region between the macula densa and the collecting duct, is morphologically and functionally heterogeneous. This heterogeneity has stymied attempts to define functional properties of individual cell types and has led to controversy concerning mechanisms and regulation of ion transport. Recently, molecular techniques have been used to identify and localize ion transport pathways along the distal tubule and to identify human diseases that result from abnormal distal tubule function. Results of these studies have clarified the roles of individual distal cell types. They suggest that the basic molecular architecture of the distal nephron is surprisingly similar in mammalian species investigated to date. The results have also reemphasized the role played by the distal tubule in regulating urinary potassium excretion. They have clarified how both peptide and steroid hormones, including aldosterone and estrogen, regulate ion transport by distal convoluted tubule cells. Furthermore, they highlight the central role that the distal tubule plays in systemic calcium homeostasis. Disorders of distal nephron function, such as Gitelman's syndrome, nephrolithiasis, and adaptation to diuretic drug administration, emphasize the importance of this relatively short nephron segment to human physiology. This review integrates molecular and functional results to provide a contemporary picture of distal tubule function in mammals.

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Reversible downregulation of thiazide diuretic receptors by acute renal ischemia

Cited by 10 publications

References 0 publications

Thiazide Diuretic Receptors in Spontaneously Hypertensive Rats and 2-Kidney 1-Clip Hypertensive Rats

Thiazide Diuretic Receptors in Spontaneously Hypertensive Rats and 2-Kidney 1-Clip Hypertensive Rats

Role of SLC12A10.2, a Na-Cl cotransporter-like protein, in a Cl uptake mechanism in zebrafish (Danio rerio)

Mammalian Distal Tubule: Physiology, Pathophysiology, and Molecular Anatomy

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