Maintenance Of Body Water Homeostasis Research Articles

Higher Expression Levels of Aquaporin Family of Proteins in the Kidneys of Arid-Desert Living Lepus yarkandensis.

Lepus yarkandensis specifically lives in arid climate with rare precipitation of Tarim Basin in western China. Aquaporins (AQPs) are a family of channel proteins that facilitate water transportation across cell membranes. Kidney AQPs play vital roles in renal tubule water permeability and maintenance of body water homeostasis. This study aimed to investigate whether kidney AQPs exhibit higher expression in arid-desert living animals. Immunohistochemistry results revealed localization of AQP1 to the capillary endothelial cells in glomerulus and epithelial cells in proximal tubule and descending thin limbs, AQP2 to the apical plasma membrane of principal cells in the cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and IMCD cells in the initial inner medullary collecting duct (IMCD1) and middle IMCD (IMCD2), and AQP3 and AQP4 to the basolateral plasma membrane of principal cells and IMCD cells in CCD, OMCD, IMCD1, and IMCD2 in L. yarkandensis kidneys. Quantitative real-time PCR analysis showed higher mRNA levels of AQP1, AQP2, AQP3, and AQP4 in L. yarkandensis kidneys compared with Oryctolagus cuniculus. Similar results were obtained by western blotting. Our results suggested that higher expression levels of AQP1, AQP2, AQP3, and AQP4 in L. yarkandensis kidneys favored for drawing more water from the tubular fluid.

Aquaporin-2 membrane targeting: still a conundrum.

The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis. In this brief review we assess the role of cyclic adenosine monophosphate (cAMP) and discuss the emerging concept that type 2 AVP receptor (V2R)-mediated AQP2 trafficking is cAMP-independent.

Dexamethasone increases aquaporin-2 protein expression in ex vivo inner medullary collecting duct suspensions.

Aquaporin-2 (AQP2) is the vasopressin-regulated water channel that controls renal water reabsorption and plays an important role in the maintenance of body water homeostasis. Excessive glucocorticoid as often seen in Cushing's syndrome causes water retention. However, whether and how glucocorticoid regulates AQP2 remains unclear. In this study, we examined the direct effect of dexamethasone on AQP2 protein expression and activity. Dexamethasone increased AQP2 protein abundance in rat inner medullary collecting duct (IMCD) suspensions. This was confirmed in HEK293 cells transfected with AQP2 cDNA. Cell surface protein biotinylation showed an increase of dexamethasone-induced cell membrane AQP2 expression and this effect was blocked by glucocorticoid receptor antagonist RU486. Functionally, dexamethasone treatment of oocytes injected with an AQP2 cRNA increased water transport activity as judged by cell rupture time in a hypo-osmotic solution (66 ± 13 s in dexamethasone vs. 101 ± 11 s in control, n = 15). We further found that dexamethasone treatment reduced AQP2 protein degradation, which could result in an increase of AQP2 protein. Interestingly, dexamethasone promoted cell membrane AQP2 moving to less buoyant lipid raft submicrodomains. Taken together, our data demonstrate that dexamethasone promotes AQP2 protein expression and increases water permeability mainly via inhibition of AQP2 protein degradation. The increase in AQP2 activity promotes water reabsorption, which may contribute to glucocorticoid-induced water retention and hypertension.

Integration of thermal and osmotic regulation of water homeostasis: the role of TRPV channels.

Maintenance of body water homeostasis is critical for preventing hyperthermia, because evaporative cooling is the most efficient means of dissipating excess body heat. Water homeostasis is achieved by regulation of water intake and water loss by the kidneys. The former is achieved by sensations of thirst that motivate water acquisition, whereas the latter is regulated by the antidiuretic action of vasopressin. Vasopressin secretion and thirst are stimulated by increases in the osmolality of the extracellular fluid as well as decreases in blood pressure and/or blood volume, signals that are precipitated by water depletion associated with the excess evaporative water loss required to prevent hyperthermia. In addition, they are stimulated by increases in body temperature. The sites and molecular mechanisms involved in integrating thermal and osmotic regulation of thirst and vasopressin secretion are reviewed here with a focus on the role of the thermal and mechanosensitive transient receptor potential-vanilloid (TRPV) family of ion channels.

Is There a Role for PGE2 in Urinary Concentration?

Prostanoids are prominent, yet complex, components in the maintenance of body water homeostasis. Recent functional and molecular studies have revealed that the local lipid mediator PGE2 is involved both in water excretion and absorption. The biologic actions of PGE2 are exerted through four different G-protein-coupled receptors; designated EP1-4, which couple to separate intracellular signaling pathways. Here, we discuss new developments in our understanding of the actions of PGE2 that have been uncovered utilizing receptor specific agonists and antagonists, EP receptor and PG synthase knockout mice, polyuric animal models, and the new understanding of the molecular regulation of collecting duct water permeability. The role of PGE2 in urinary concentration comprises a variety of mechanisms, which are not fully understood and likely depend on which receptor is activated under a particular physiologic condition. EP3 and microsomal PG synthase type 1 play a role in decreasing collecting duct water permeability and increasing water excretion, whereas EP2 and EP4 can bypass vasopressin signaling and increase water reabsorption through two different intracellular signaling pathways. PGE2 has an intricate role in urinary concentration, and we now suggest how targeting specific prostanoid receptor signaling pathways could be exploited for the treatment of disorders in water balance.

Lixivaptan: a novel vasopressin receptor antagonist

Arginine vasopressin, also known as antidiuretic hormone, is a neuropeptide that functions in the maintenance of body water homeostasis. Inappropriate secretion of vasopressin has been implicated in the pathophysiology of multiple diseases, including polycystic kidney disease, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and the hyponatremia commonly associated with cirrhosis and congestive heart failure. Vasopressin receptor antagonists are novel agents that block the physiologic actions of vasopressin. Lixivaptan is a vasopressin receptor antagonist with high V2 receptor affinity and is now undergoing Phase III clinical trials. Studies so far have demonstrated that lixivaptan is efficacious in the correction of hyponatremia in SIADH, heart failure and liver cirrhosis with ascites, and few adverse effects have been noted. Thus, lixivaptan remains a promising therapeutic modality for the treatment of multiple diseases and prevention of the associated morbidity and mortality associated with hyponatremia.

Vasopressin-independent mechanisms in controlling water homeostasis

The maintenance of body water homeostasis depends on the balance between water intake and water excretion. In the kidney, vasopressin (Vp) is a critical regulator of water homeostasis by controlling the insertion of aquaporin 2 (AQP2) onto the apical membrane of the collecting duct principal cells in the short term and regulating the gene expression of AQP2 in the long term. A growing body of evidence from both in vitro and in vivo studies demonstrated that both secretin and oxytocin are involved as Vp-independent mechanisms regulating the renal water reabsorption process, including the translocation and expression of AQP2. This review focuses on how these two hormones are potentially involved as Vp-independent mechanisms in controlling water homeostasis.

Aquaporin-2 abundance in the renal collecting duct: new insights from cultured cell models

The renal cortico-papillary osmotic gradient is generated by sodium reabsorption in the thick ascending limb. The antidiuretic hormone arginine vasopressin (AVP) increases collecting duct water permeability by enhancing aquaporin-2 (AQP2) water channel insertion in the apical membrane of principal cells, allowing water to passively flow along the osmotic gradient from the tubule lumen to the interstitium. In addition to short-term AQP2 redistribution between intracellular compartments and the cell surface, AQP2 whole cell abundance is tightly regulated. AVP is a major transcriptional activator of the AQP2 gene, and stimulation of insulin- and calcium-sensing receptors respectively potentiate and reduce its action. Extracellular tonicity is another key factor that determines the levels of AQP2 abundance. Its effect is dependent on activation of the tonicity-responsive enhancer binding protein that reinforces AVP-induced AQP2 transcriptional activation. Conversely, activation of the NF-kappaB transcriptional factor by proinflammatory factors reduces AQP2 gene transcription. Aldosterone additionally regulates AQP2 whole cell abundance by simultaneously reducing AQP2 gene transcription and stimulating AQP2 mRNA translation. These examples illustrate how cross talk between various stimuli regulates AQP2 abundance in collecting duct principal cells and consequently contributes to maintenance of body water homeostasis.

Bypassing Vasopressin Receptor Signaling Pathways in Nephrogenic Diabetes Insipidus

Water reabsorption in the kidney represents a critical physiological event in the maintenance of body water homeostasis. This highly regulated process relies largely on vasopressin (VP) action and on the VP-sensitive water channel (AQP2) that is expressed in principal cells of the kidney collecting duct. Defects in the VP signaling pathway and/or in AQP2 cell surface expression can lead to an inappropriate reduction in renal water reabsorption and the development of nephrogenic diabetes insipidus, a disease characterized by polyuria and polydipsia. This review focuses on the major regulatory steps that are involved in AQP2 trafficking and function. Specifically, we begin with a discussion on VP-receptor-independent mechanisms of AQP2 trafficking, with special emphasis on the nitric oxide-cyclic guanosine monophosphate signaling pathway, followed by a review of the mechanisms that govern AQP2 endocytosis and exocytosis. We then discuss emerging data illustrating roles played by the actin cytoskeleton on AQP2 trafficking, and lastly we consider elements that affect AQP2 protein expression in cells. Recent advances in each topic are summarized and are presented in the context of their potential to serve as a basis for the development of novel therapies that may ultimately improve life quality of nephrogenic diabetes insipidus patients.

Aquaporin 2 Mutations in Nephrogenic Diabetes Insipidus

Water reabsorption in the renal collecting duct is regulated by the antidiuretic hormone vasopressin (AVP). When the vasopressin V2 receptor, present on the basolateral site of the renal principal cell, becomes activated by AVP, aquaporin-2 (AQP2) water channels will be inserted in the apical membrane, and in this fashion, water can be reabsorbed from the pro-urine into the interstitium. The essential role of the vasopressin V2 receptor and AQP2 in the maintenance of body water homeostasis became clear when it was shown that mutations in their genes cause nephrogenic diabetes insipidus, a disorder in which the kidney is unable to concentrate urine in response to AVP. This review describes the current knowledge on AQP2 mutations in nephrogenic diabetes insipidus.