Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The discovery of water channels (aquaporins) was a breakthrough in research on water transport. Aquaporins are a family of intrinsic membrane proteins that function as water-selective channels (except aquaporin-3 and aquaporin-7, which are permeable to urea and glycerol as well) in the plasma membranes of many cells. Aquaporin-0 (MIP26) functions to maintain fluid balance in the lens. Aquaporin-1 is involved in water reabsorption in the kidney's proximal tubules and the thin descending Henle's loop, aqueous humor formation in eye, cerebrospinal fluid formation in brain, and airway hydration in lung. Aquaporin-2 is the only water channel that is activated by vasopressin to enhance water reabsorption in the kidney collecting duct. Aquaporin-3 also contributes to water reabsorption in the kidney collecting duct but is unresponsive to vasopressin. It also appears that aquaporin-3 may contribute to cornea transparency. Aquaporin-4 is involved in cerebrospinal fluid transport in brain, water transport in the kidney collecting duct, aqueous humor transport in the eye, and airway hydration in the lung. Aquaporin-5 apparently is coupled to fluid secretion in exocrine tissues. Although the exact function of aquaporin-6 is not known due to its uncertain localization, its restricted presence in the kidney may suggest a potential role in water transport. Aquaporin-7 appears to play a role in the cryopreservation of the sperm whereas aquaporin-8 is responsible for the secretion of pancreatic juice. The major focus of this review is a discussion of aquaporins in renal epithelia, and particularly the mechanisms associated with vasopressin-mediated water transport involving aquaporin-2 and the signal transduction pathways linked to vasopressin action.
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PMID:Aquaporins (water channels): role in vasopressin-activated water transport. 982 41

Previously, we demonstrated that escape from vasopressin-induced antidiuresis ("vasopressin escape") in rats is associated with a large, selective decrease in whole kidney expression of aquaporin-2, the vasopressin-regulated water channel. Here, we show that isolated perfused inner medullary collecting ducts (IMCDs) from vasopressin-escape rats desamino-[D-arginine]vasopressin (DDAVP)/water-loaded have dramatically reduced vasopressin-dependent osmotic water permeabilities [46% of control rats (DDAVP alone)], which coincides with a fall in inner medullary aquaporin-2 protein abundance as measured by immunoblotting in the opposite kidney. Furthermore, we demonstrate in IMCD suspensions that cAMP accumulation in response to DDAVP is substantially reduced in the vasopressin-escape rats both in the presence and absence of the phosphodiesterase inhibitor IBMX. By immunoblotting, we show that the abundance of two proteins important in cAMP generation: the stimulatory heterotrimeric G protein subunit Gs and adenylyl cyclase type VI, do not change. We conclude that vasopressin escape is associated with relative vasopressin resistance of the collecting duct cells manifested by decreased intracellular cAMP levels. The decreased cAMP levels can contribute to the demonstrated decrease in collecting duct water permeability in two ways: 1) by causing a decrease in aquaporin-2 expression and 2) by limiting the acute action of vasopressin to increase collecting duct water permeability.
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PMID:Escape from vasopressin-induced antidiuresis: role of vasopressin resistance of the collecting duct. 984 9

Several K+ conductances have been identified in the kidney, with specific properties and localization in distinct cell types and membrane domains. On the other hand, several K+ channels have been characterized at the molecular level. By immunolocalization, we show that a new inward rectifying K+ channel, TWIK-1, is specifically expressed in distinct tubular segments and cell types of the rat kidney. In the proximal tubule, TWIK-1 prevails in the initial portions (convoluted part), where it is restricted to the apical (brush-border) membrane. In the collecting duct, immunofluorescence was intracellular or confined to the apical membrane and restricted to intercalated cells, i.e., in cells lacking aquaporin-2, as shown by double immunofluorescence. TWIK was also expressed in medullary and cortical parts of the thick limb of the loop of Henle, identified with an anti-Tamm-Horsfall protein antibody (double immunofluorescence). The intensity of TWIK-1 immunolabeling was unchanged in rats fed a low-Na+ or a low-K+ diet. Because TWIK-1 shares common properties with the low-conductance apical K+ channel of the collecting duct, we propose that it could play a role in K+ secretion, complementary to ROMK, another recently characterized K+ channel located in principal cells of the cortical collecting duct and in the loop of Henle.
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PMID:Expression of TWIK-1, a novel weakly inward rectifying potassium channel in rat kidney. 984 22

Hypercalcemia is frequently associated with a urinary concentrating defect and overt polyuria. The molecular mechanisms underlying this defect are poorly understood. Dysregulation of aquaporin-2 (AQP2), the predominant vasopressin-regulated water channel, is known to be associated with a range of congenital and acquired water balance disorders including nephrogenic diabetes insipidus and states of water retention. This study examines the effect of hypercalcemia on the expression of AQP2 in rat kidney. Rats were treated orally for 7 d with dihydrotachysterol, which produced significant hypercalcemia with a 15 +/- 2% increase in plasma calcium concentration. Immunoblotting and densitometry of membrane fractions revealed a significant decrease in AQP2 expression in kidney inner medulla of hypercalcemic rats to 45.7 +/- 6.8% (n = 11) of control levels (100 +/- 12%, n = 9). A similar reduction in AQP2 expression was seen in cortex (36.9 +/- 4.2% of control levels, n = 6). Urine production increased in parallel, from 11.3 +/- 1.4 to a maximum of 25.3 +/- 1.9 ml/d (P < 0.01), whereas urine osmolality decreased from 2007 +/- 186 mosmol/kg x H2O to 925 +/- 103 mosmol/kg x H2O (P < 0.01). Immunocytochemistry confirmed a decrease in total AQP2 labeling of collecting duct principal cells from kidneys of hypercalcemic rats, and reduced apical labeling. Immunoelectron microscopy demonstrated a significant reduction in AQP2 labeling of the apical plasma membrane, consistent with the development of polyuria. In summary, the results strongly suggest that AQP2 downregulation and reduced apical plasma membrane delivery of AQP2 play important roles in the development of polyuria in association with hypercalcemia.
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PMID:Decreased aquaporin-2 expression and apical plasma membrane delivery in kidney collecting ducts of polyuric hypercalcemic rats. 984 72

The aquaporin-2 promoter has been used to drive Cre recombinase expression in order to achieve renal collecting duct principal cell specific gene deletion. This technique requires two lines of mice: one transgenic mouse line containing a cell-specific promoter driving Cre recombinase expression and the other line, engineered using gene targeting strategies, that contains a lox-flanked target gene of interest. Mating of these two mouse lines permits cell-specific deletion of the target gene. This method could ultimately be used to obtain targeted deletion of any gene in any cell type in the kidney for which a specific promoter has been identified. The applications of this technology, as well as its strengths and weaknesses, are discussed with particular reference to the kidney.
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PMID:Targeting collecting tubules using the aquaporin-2 promoter. 989 17

In the renal collecting duct, vasopressin acutely activates cAMP production, resulting in trafficking of aquaporin-2 water channels (AQP2) to the apical plasma membrane, thereby increasing water permeability. This acute response is modulated by long-term changes in AQP2 expression. Recently, a cAMP-responsive element has been identified in the AQP2 gene, raising the possibility that changes in cAMP levels may control AQP2 expression. To investigate this possibility, we determined AQP2 protein levels in a strain of mice, DI +/+ severe (DI), which have genetically high levels of cAMP-phosphodiesterase activity, and hence low cellular cAMP levels, and severe polyuria. Semiquantitative immunoblotting of membrane fractions prepared from whole kidneys revealed that AQP2 levels in DI mice were only 26 +/- 7% (+/-SE) of those in control mice (n = 10, P < 0.01). In addition, semiquantitative Northern blotting revealed a significantly lower AQP2 mRNA expression in kidneys from DI mice compared with control mice (43 +/- 6% vs. 100 +/- 10%; n = 6 in each group, P < 0.05). AQP3 levels were also reduced. The mice were polyuric and urine osmolalities were accordingly substantially lower in the DI mice than in controls (496 +/- 53 vs. 1,696 +/- 105 mosmol/kgH2O, respectively). Moreover, there was a linear correlation between urine osmolalities and AQP2 levels (P < 0.05). Immunoelectron microscopy confirmed the markedly lower expression of AQP2 in collecting duct principal cells in kidneys of DI mice and, furthermore, demonstrated that AQP2 was almost completely absent from the apical plasma membrane. Thus expression of AQP2 and AQP2 trafficking were severely impaired in DI mice. These results are consistent with the view that in vivo regulation of AQP2 expression by vasopressin is mediated by cAMP.
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PMID:Low aquaporin-2 levels in polyuric DI +/+ severe mice with constitutively high cAMP-phosphodiesterase activity. 995 Sep 48

The antidiuretic hormone arginine-vasopressin (AVP) regulates water reabsorption in renal collecting duct principal cells by inducing a cAMP-dependent translocation of water channels (aquaporin-2, AQP-2) from intracellular vesicles into the apical cell membranes. In subcellular fractions from primary cultured rat inner medullary collecting duct (IMCD) cells, enriched for intracellular AQP-2-bearing vesicles, catalytic protein kinase A (PKA) subunits and several protein kinase A anchoring proteins (AKAPs) were detected. In nonstimulated IMCD cells the majority of AQP-2 staining was detected intracellularly but became mainly localized within the cell membrane after stimulation with AVP or forskolin. Quantitative analysis revealed that preincubation of the cells with the synthetic peptide S-Ht31, which prevents the binding between AKAPs and regulatory subunits of PKA, strongly inhibited AQP-2 translocation in response to forskolin. Preincubation of the cells with the PKA inhibitor H89 prior to forskolin stimulation abolished AQP-2 translocation. In contrast to H89, S-Ht31 did not affect the catalytic activity of PKA. These data demonstrate that not only the activity of PKA, but also its tethering to subcellular compartments, are prerequisites for cAMP-dependent AQP-2 translocation.
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PMID:Protein kinase A anchoring proteins are required for vasopressin-mediated translocation of aquaporin-2 into cell membranes of renal principal cells. 998 36

In animal models of the syndrome of inappropriate antidiuresis (SIADH), sustained administration of vasopressin and water results in free-water retention and progressive hyponatremia for several days, which is then followed by escape from the vasopressin-induced antidiuresis. With the onset of vasopressin escape, water excretion increases despite sustained administration of vasopressin, allowing water balance to be re-established and the serum sodium to be stabilized at a steady, albeit decreased, level. Studies from our laboratories have investigated whether this escape phenomenon can be attributed to altered regulation of aquaporin water channels. After four-day pre-treatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic minipump, rats were divided into control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load) groups. A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating escape from antidiuresis. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein (measured by semi-quantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. Additional studies have indicated that the observed down-regulation of aquaporin-2 expression also occurs in the renal cortex as well as the inner and outer medullas, and can be reversed simply by water restriction despite maintenance of hyponatremia. Our results therefore suggest that escape from vasopressin-induced antidiuresis is attributable, at least in part, to a vasopressin-independent and osmolality-independent decrease in aquaporin-2 water channel expression in the renal collecting duct. Similar mechanisms likely contribute to the phenomenon of escape from antidiuresis seen clinically in patients with SIADH as well.
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PMID:Studies of renal aquaporin-2 expression during renal escape from vasopressin-induced antidiuresis. 1002 31

Hyponatremia is common in advanced heart failure and relates to the severity of the disease. Non-osmotic arginine vasopressin (AVP) release and biosynthesis have been shown to be increased during chronic cardiac failure (CHF) and baroreceptors pathways have been demonstrated to play a major role in this non-osmotic stimulation of AVP. Decreased cardiac output unloads the baroreceptors and activates the sympathetic nervous system, thus stimulating AVP through a separate pathway which overrides the osmotic pathway. Besides sympathetic nervous system activation, neurohumoral peptides, such as angiotensin II, endothelins, natriuretic peptides and prostaglandins, could also participate in the non-osmotic AVP activation. The vasoconstrictor effect of AVP has been supported by the decrease systemic vascular resistance during the administration of V1 receptor AVP antagonist in CHF patients. Administration of V2 receptor AVP antagonists corrects the hyponatremia and has been demonstrated to improve survival in animal models of heart failure. Preliminary data in humans with CHF also demonstrate urinary dilution and correction of hyponatremia with orally active non-peptide V2 receptor antagonists. Finally, upregulation of the AVP-regulated water channels, aquaporin-2 (AQP2), located in the collecting duct cells has been shown in experimental heart failure. This AQP2 upregulation can be entirely suppressed by V2 receptor AVP antagonists paralleling the correction of the hyponatremia. Thus, non-osmotic release of AVP in CHF upregulates AQP2 water channels, enhances water reabsorption and causes hyponatremia. The V1, and perhaps the V2, receptor activation may also diminish cardiac function.
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PMID:Recent advances in the understanding of water metabolism in heart failure. 1002 33

The discovery of the aquaporin family of water channels has greatly improved our understanding of how water crosses epithelial cells, particularly in the kidney. The study of the mechanisms involved in the regulation of collecting duct water permeability, in particular, has advanced very rapidly since the identification and characterization of aquaporin-2 (AQP2) in 1993. One of the more surprising findings has been the dramatic long-term changes that are seen in the abundance of this protein, as well as the recognition that these changes represent a way of modulating the acute antidiuretic effects of vasopressin. Furthermore, such changes seem to be of etiological and pathological significance in a number of clinical disorders of water balance. This review focuses on the various conditions in which AQP2 expression is altered (either increased or decreased) and on what this can tell us about the signals and mechanisms controlling these changes. Ultimately, this may be of great value in the clinical management of water balance disorders. Evidence is also now beginning to emerge that there are similar changes in the expression of other renal aquaporins, which had previously been thought to provide an essentially constitutive water permeability pathway, suggesting that they too should be considered as regulatory factors in the control of body water balance.
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PMID:Long-term regulation of aquaporins in the kidney. 1007 Jan 56


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