Urea transporter UT-A1 and aquaporin-2 proteins decrease in response to angiotensin II or norepinephrine-induced acute hypertension

Klein, Janet D.; Murrell, Brian P.; Tucker, Suzanne; Kim, Young‐Hee; Sands, Jeff M.

doi:10.1152/ajprenal.00173.2006

Cited by 40 publications

(40 citation statements)

References 21 publications

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“…The inner medullary collecting duct also becomes more permeable to urea, a reaction that is catalyzed by PKA and mediated by the activation of an AVP-regulated urea transporter (60). In addition, hormone binding of V2Rs stimulates ENaC activity and leads to an increase in Na ϩ transport in the thick ascending limb and collecting duct (4).…”

Section: Distribution and Function Of V2rsmentioning

confidence: 99%

The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors

Juul

Bichet

Nielsen

et al. 2014

American Journal of Physiology-Renal Physiology

124

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Juul KV, Bichet DG, Nielsen S, Nørgaard JP. The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors. Am J Physiol Renal Physiol 306: F931-F940, 2014. First published March 5, 2014 doi:10.1152/ajprenal.00604.2013.-The arginine vasopressin (AVP) type 2 receptor (V2R) is unique among AVP receptor subtypes in signaling through cAMP. Its key function is in the kidneys, facilitating the urine concentrating mechanism through the AVP/V2 type receptor/aquaporin 2 system in the medullary and cortical collecting ducts. Recent clinical and research observations strongly support the existence of an extrarenal V2R. The clinical importance of the extrarenal V2R spans widely from stimulation of coagulation factor in the endothelium to as yet untested potential therapeutic targets. These include V2R-regulated membranous fluid turnover in the inner ear, V2R-regulated mitogensis and apoptosis in certain tumor tissues, and numerous other cell types where the physiological role of V2Rs still requires further research. Here, we review current evidence on the physiological and pathophysiological functions of renal and extrarenal V2Rs. These functions of V2R are important, not only in rare diseases with loss or gain of function of V2R but also in relation to the recent use of nonpeptide V2R antagonists to treat hyponatremia and possibly retard the growth of cysts and development of renal failure in autosomal dominant polycystic kidney disease. The main functions of V2R in principal cells of the collecting duct are water, salt, and urea transport by modifying the trafficking of aquaporin 2, epithelial Na ϩ channels, and urea transporters and vasodilation and stimulation of coagulation factor properties, mainly seen with pharmacological doses of 1-desamino-8-D-AVP. The AVPR2 gene is located on the X chromosome, in a region with high probability of escape from inactivation; this may lead to phenotypic sex differences, with females expressing higher levels of transcript than males. vasopressin V 2 receptor; arginine vasopressin V2 receptor; arginine vasopressin; desmopressin; extrarenal vasopressin V 2 receptor THE PURPOSE OF THIS REPORT is to review current evidence on the physiological and pathophysiogical functions of renal and extrarenal arginine vasopressin (AVP) type 2 receptors, referred to as V2Rs (Fig. 1).AVP is an important neurohypophyseal nonapeptide that, via its three receptor types, is primarily responsible for regulating osmotic homeostasis of body fluids, volume homeostasis, and vasoconstriction in addition to an array of central functions such as memory and learning (17,29). In addition to these endocrine functions, AVP also contributes to regulating mitogenesis, cell survival, and death (apoptosis) (77).AVP is released from its storage site in the posterior pituitary (Fig. 2) by highly sensitive osmotic stimuli, specifically by a Ͻ1-2% increase in plasma osmolarity, as originally detailed in the 1940s through classic research by Prof. E. B. Verney (125). AVP release may also ...

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Section: Distribution and Function Of V2rsmentioning

confidence: 99%

The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors

Juul

Bichet

Nielsen

et al. 2014

American Journal of Physiology-Renal Physiology

124

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“…Therefore, it is pertinent to ask whether changes in ECF volume or tonicity are associated with regulation of urea transporters. Indeed, urea transporter expression was found to be downregulated in aldosterone-induced ECF volume expansion (72), in ECF volume expansion that is associated with nephrotic syndrome (73), in obese Zucker rats with type 2 diabetes and hypertension (74), in response to hypertension induced by angiotensin II or norepinephrine (75), and in an animal model of the syndrome of inappropriate antidiuresis (76). These decreases in urea transporter expression potentially could be a homeostatic response to ECF volume expansion or hypertension, increasing NaCl and water excretion via ureainduced osmotic diuresis.…”

Section: Possible Role Of Urea Transporters In Regulation Of Extracelmentioning

confidence: 99%

Urea and Renal Function in the 21st Century

Fenton¹,

Knepper²

2007

Journal of the American Society of Nephrology

115

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Since the turn of the 21st century, gene knockout mice have been created for all major urea transporters that are expressed in the kidney: the collecting duct urea transporters UT-A1 and UT-A3, the descending thin limb isoform UT-A2, and the descending vasa recta isoform UT-B. This article discusses the new insights that the results from studies in these mice have produced in the understanding of the role of urea in the urinary concentrating mechanism and kidney function. Following is a summary of the major findings: (1) Urea accumulation in the inner medullary interstitium depends on rapid transport of urea from the inner medullary collecting duct (IMCD) lumen via UT-A1 and/or UT-A3; (2) as proposed by Robert Berliner and colleagues in the 1950s, the role of IMCD urea transporters in water conservation is to prevent a urea-induced osmotic diuresis; (3) the absence of IMCD urea transport does not prevent the concentration of NaCl in the inner medulla, contrary to what would be predicted from the passive countercurrent multiplier mechanism in the form proposed by Kokko and Rector and Stephenson; (4) deletion of UT-B (vasa recta isoform) has a much greater effect on urinary concentration than deletion of UT-A2 (descending limb isoform), suggesting that the recycling of urea between the vasa recta and the renal tubules quantitatively is less important than classic countercurrent exchange; and (5) urea reabsorption from the IMCD and the process of urea recycling are not important elements of the mechanism of protein-induced increases in GFR. In addition, the clinical relevance of these studies is discussed, and it is suggested that inhibitors that specifically target collecting duct urea transporters have the potential for clinical use as potassium-sparing diuretics that function by creation of urea-dependent osmotic diuresis.

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“…Ϫ has been reported in response to 7-or 14-day administration of angiotensin II in Sprague-Dawley rats (9). But no change in the abundances of these three proteins has been observed in wildtype mice that received the same treatment with angiotensin II (15).…”

Section: Discussionmentioning

confidence: 98%

Role of protein kinase C-α in hypertonicity-stimulated urea permeability in mouse inner medullary collecting ducts

Wang

Klein

Froehlich

et al. 2013

American Journal of Physiology-Renal Physiology

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The kidney's ability to concentrate urine is vitally important to our quality of life. In the hypertonic environment of the kidney, urea transporters must be regulated to optimize function. We previously showed that hypertonicity increases urea permeability and that the protein kinase C (PKC) blockers chelerythrine and rottlerin decreased hypertonicity-stimulated urea permeability in rat inner medullary collecting ducts (IMCDs). Because PKCα knockout (PKCα−/−) mice have a urine-concentrating defect, we tested the effect of hypertonicity on urea permeability in isolated perfused mouse IMCDs. Increasing the osmolality of perfusate and bath from 290 to 690 mosmol/kgH2O did not change urea permeability in PKCα−/− mice but significantly increased urea permeability in wild-type mice. To determine whether the response to protein kinase A was also missing in IMCDs of PKCα−/− mice, tubules were treated with vasopressin and subsequently with the PKC stimulator phorbol dibutyrate (PDBu). Vasopressin stimulated urea permeability in PKCα−/− mice. Like vasopressin, forskolin stimulated urea permeability in PKCα−/− mice. We previously showed that, in rats, vasopressin and PDBu have additive stimulatory effects on urea permeability. In contrast, in PKCα−/− mice, PDBu did not further increase vasopressin-stimulated urea permeability. Western blot analysis showed that expression of the UT-A1 urea transporter in IMCDs was increased in response to vasopressin in wild-type mice as well as PKCα−/− mice. Hypertonicity increased UT-A1 phosphorylation in wild-type mice but not in PKCα−/− mice. We conclude that PKCα mediates hypertonicity-stimulated urea transport but is not necessary for vasopressin stimulation of urea permeability in mouse IMCDs.

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Urea transporter UT-A1 and aquaporin-2 proteins decrease in response to angiotensin II or norepinephrine-induced acute hypertension

Cited by 40 publications

References 21 publications

The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors

The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors

Urea and Renal Function in the 21st Century

Role of protein kinase C-α in hypertonicity-stimulated urea permeability in mouse inner medullary collecting ducts

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