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)

Aquaporins are proteins that mediate transmembrane water transport in a variety of tissues including the kidney. Vasopressin plays an important role in regulation of water metabolism, and under normal conditions the kidney collecting duct is extremely sensitive to vasopressin. Vasopressin stimulates the synthesis of aquaporin 2 (AQP2) in kidney collecting duct principal cells. Studies in Brattle Boro rats which are vasopressin deficient, revealed low levels of AQP2 in association with extreme polyuria. After vasopressin treatment for 5 days AQP2 levels increased threefold. Using rat models with nephrogenic diabetes insipidus (NDI) we have demonstrated that AQP2 expression is down regulated in association with polyuria, suggesting that reduced levels of AQP2 may be a general factor in acquired forms of NDI from a variety of reasons. The polyuria and urinary concentrating defects associated with an abnormal nightly-increase in AVP in patients with nocturnal enuresis may partly be due to a lack of vasopressin-mediated AQP2 expression since treatment with desmopressin in these patients have normalised their nocturnal urine production.
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PMID:Do aquaporins have a role in nocturnal enuresis? 916 2

By using immunocytochemical techniques we have been able to localize the V1 vasopressin receptor in the rat kidney. Immunoblotting using an antiserum raised against an affinity-purified vasopressin receptor showed a 55,000 daltons protein band that has a molecular mass similar to that of the liver V1 vasopressin receptor, as demonstrated by cross-linking studies. Immunoblotting of the antibody showed a band of 55,000 daltons in A-10 cells, which contains the V1 subtype, whereas it did not stain LLC-PK1 cells, which possess the V2 subtype, showing that the antibody recognizes the V1 vasopressin receptor. The immunostaining of kidney sections with this antiserum showed a strong reaction of the connecting tubules and cortical and medullary collecting ducts. The immunostaining pattern of connecting tubule and collecting duct cells was different, that is, the former showed a staining of both the apical and basal plasma membrane but also in the cytoplasm, whereas the latter showed a strong reaction mainly in the basolateral membrane. Immunostaining of consecutive serial sections with an antiserum raised against tissue kallikrein, an enzyme present exclusively in connecting tubules, and with the anti-receptor serum allowed us to show, for the first time, the presence of the vasopressin receptor in the connecting tubule cells and their absence in intercalated cells, the other cell type present in connecting tubules. These findings support experiments carried in the eighties on the release of renal tissue kallikrein by AVP.
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PMID:Immunolocalization of V1 vasopressin receptors in the rat kidney using anti-receptor antibodies. 935 Jun 43

The kidney provides an important contribution to permit the fetus to successfully transition to an independent existence by production of urine with significantly different osmolality compared with plasma. Although recent work has uncovered many aspects of the maturation and regulation of the renal concentrating and diluting mechanism, understanding of how alterations in the expression of aquaporin (AQP) water channels contribute to the formation of urine in the perinatal period is incomplete. Here, we report that both AQP-2 and -3 are expressed during fetal life as early as embryonic d 18 in ureteric buds of rat kidneys, where each is localized to the apical and basolateral membranes of epithelial cells, respectively. Northern analyses demonstrate that the 1.9-kb AQP-2 transcript is present in fetal and postnatal rat kidneys similar to that observed in adults. AQP-2 mRNA expression increases after d 3 of postnatal life. Immunoblotting reveals an increase in total kidney AQP-2 protein particularly with respect to its glycosylated form after postnatal d 3. AQP-3 protein also exhibits a similar alteration likely due to a similar increase in its glycosylation state. Both AQP-2 and AQP-3 display a distribution in the collecting ducts of human postnatal infants and adults identical to that exhibited in rat kidneys. These data show that both AQP-2 and -3 are present in collecting duct epithelia of fetal and postnatal kidneys. Thus, the reduced AVP-responsiveness and decreased urinary concentrating ability of the kidney during the fetal and immediate postnatal period does not appear to be caused by lack of AQP-2 or AQP-3 proteins.
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PMID:The perinatal expression of aquaporin-2 and aquaporin-3 in developing kidney. 962 88

In the rat cortical collecting duct (CCD), epinephrine inhibits vasopressin (AVP)-dependent water permeability and Na+ reabsorption. Although inhibition is reversed by the alpha2-adrenoceptor (AR) antagonist yohimbine, suggesting the epinephrine effect is primarily mediated by an alpha2-AR [C. T. Hawk, L. H. Kudo, A. J. Rouch, and J. A. Schafer. Am. J. Physiol. 265 (Renal Fluid Electrolyte Physiol. 34): F449-F460, 1993], there are also suggestions of an effect at an additional receptor, perhaps an alpha1-AR. For the present experiments, we used RT-PCR of total RNA extracted from 1 to 5 mm of microdissected CCDs from rat kidney to identify the alpha-AR isoforms expressed. Specific primers for the alpha2-ARs amplifying from the 6th transmembrane (TM) to the 3'-untranslated regions, revealed the presence of alpha2A and alpha2B. Western blot analysis also indicated the presence of alpha2B-AR at the protein level. Degenerate alpha1-AR primers that amplify from conserved regions of TM-1 to TM-5, as well as specific primers that amplify either the same region (alpha1B), the carboxy terminus (alpha1A), or within the third cytoplasmic loop (alpha1D), indicated the presence of all three alpha1-ARs. Measurement of transepithelial voltage in isolated perfused renal tubules indicated a small inhibitory effect mediated by alpha1-ARs. Although the functional effects of epinephrine on AVP-dependent transport processes appear to be mediated predominantly by an alpha2-AR, a small contribution to the overall alpha-AR effect may be due to simultaneous activation of an alpha1-AR.
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PMID:Expression of multiple alpha-adrenoceptor isoforms in rat CCD. 968 12

Vasopressin (AVP) is released in response to both osmotic and nonosmotic stimuli. Nonosmotic-stimulated AVP release occurs in cardiac failure, cirrhosis, and pregnancy in response to alterations in arterial circulatory integrity. Cardiac failure in rats is associated with increased plasma AVP and hypothalamic AVP mRNA, and in humans, it is associated with cardiac failure. Plasma AVP concentrations are elevated when measured with a sensitive radioimmunoassay. Urinary concentrations of AVP-responsive aquaporin-2 water channels are also elevated in cardiac failure. V2 receptor antagonists correct the impaired solute-free water excretion seen in rats with low-output cardiac failure and reverse the upregulation of renal aquaporin-2 water channels. Orally active non-peptide-selective V2 receptor antagonists administered to patients with congestive cardiac failure decrease urinary concentrations of aquaporin-2, increase solute-free water clearance, and correct the hyponatremia. Cirrhosis of the liver results in splanchnic arterial vasodilation and increased vascular capacity, most likely secondary to increased nitric oxide production. This relative underfilling of the arterial circulation stimulates nonosmotic AVP release with resultant water retention. Aquaporin-2 gene expression is upregulated in the kidneys of rats with cirrhosis of the liver. AVP-2 receptor antagonists administered to animals with cirrhosis reverse the water retention. Human studies using orally active, non-peptide-selective V2 receptor antagonists in patients with cirrhosis are currently underway. Pregnancy is another state of nitric oxide-mediated arterial vasodilation that is associated with plasma AVP concentrations that are relatively high for the degree of hypoosmolality. Upregulation of the water channel aquaporin-2 in the renal papillae of pregnant rats has also been demonstrated, and this effect is reversed by administration of a V2 receptor antagonist.
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PMID:Vasopressin release, water channels, and vasopressin antagonism in cardiac failure, cirrhosis, and pregnancy. 975 91

While in vivo data suggests that diuretics such as furosemide and hydrochlorothiazide alter inner medulla collecting duct (IMCD) cell electrolyte transport, this has not been confirmed by in vivo studies nor have the mechanisms been evaluated. This study evaluated the direct effect of these diuretics as well as amiloride on sodium and chloride unidirectional permeability in the isolated perfused rat IMCD. In the absence of diuretics, the permeability of sodium was lower than that of chloride (0.63 +/- 0.05 compared with 0.83 +/- 0.08 micrometer/s), although both were relatively impermeable when compared to water. Furosemide (10(-4)) and hydrochlorothiazide (10(-3)) both increased the diffusional permeability of chloride by approximately 30% (0.80 +/- 0.06 to 1.04 +/- 0.09 micrometer/s, p < 0.01, and 0.74 +/- 0.09 to 0.98 +/- 0.10 micrometer/s, p < 0.02, respectively). However, sodium permeability was unaltered. Inhibition of Na+, K+-ATPase by ouabain or cooling (4 degrees C) inhibited basal sodium but not chloride permeability while a maximal antidiuretic AVP concentration did not alter sodium or chloride permeability. However, increasing the lumen and bath sodium chloride concentration from 150 to 300 and 600 mM significantly increased both sodium and particularly chloride conductance. In contrast, amiloride (10(-4)) significantly reduced both sodium and chloride permeability. These studies support a direct effect of furosemide and hydrochlorothiazide on the IMCD and suggest that their in vivo effect is primarily mediated by facilitating the passive movement of chloride into the lumen via a favourable electrochemical gradient. These results also demonstrate that amiloride inhibits both sodium and chloride unidirectional permeability by mechanisms separate to that of the sulphonamide-related diuretics.
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PMID:Effect of diuretics on sodium and chloride permeability in the rat papillary collecting duct. 976 78

We reported previously [Am. J. Physiol. 271 (Renal Fluid Electrolyte Physiol. 40): F391-F400, 1996] that dopamine inhibits vasopressin (AVP)-dependent water permeability and Na+ transport in the rat cortical collecting duct (CCD) apparently through a D4 dopamine receptor. The present experiments used RT-PCR of total RNA extracted from microdissected rat CCD to determine whether the D4 and D1A dopamine receptor isoforms are expressed. Specific primers were used to amplify three regions of the D4 cDNA. All three gave products with 98-100% nucleotide identity to the known rat D4 sequence; however, there was an extra 6-bp insert at the 3' end of the second transmembrane region that was identical to the human and mouse sequences but which had not been documented in the rat sequence. D4 receptor protein was also localized exclusively to the CCD and medullary collecting ducts by immunohistochemistry. Two regions of the D1A dopamine receptor message were also amplified by RT-PCR of RNA from rat CCD and were verified by sequencing and immunohistochemistry. We conclude that both D4 and D1A dopamine receptors are expressed in the rat CCD, but the physiological effects are attributable to a D4 receptor.
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PMID:Dopamine D4 receptor isoform mRNA and protein are expressed in the rat cortical collecting duct. 981 31

Vasopressin or AVP regulates water reabsorption by the kidney inner medullary collecting duct (IMCD) through the insertion and removal of aquaporin (AQP) 2 water channels into the IMCD apical membrane. AVP-elicited trafficking of AQP2 with the apical membrane occurs via a specialized population of vesicles that resemble synaptic vesicles in neurons. AQP2 vesicles and the IMCD apical membrane contain homologs of vesicle-targeting and signal transduction proteins found in neurons. Expression studies of AQP2, including human AQP2 mutants, suggest that the carboxyl-terminal domain of AQP2 is important in AQP2 trafficking, particularly as a site for cAMP-dependent protein kinase phosphorylation. These present data reveal that IMCD cells possess a complex integrated-signaling and vesicle-trafficking machinery that provides integration of AVP-elicited water transport with many other parameters within the IMCD cell as well as kidney.
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PMID:Modulation of vasopressin-elicited water transport by trafficking of aquaporin2-containing vesicles. 1009 6

We have previously shown that a chronic reduction in plasma vasopressin level slowed the progression of chronic renal failure (CRF) in Sprague Dawley rats. The aim of the present study was to determine the respective contribution of pressor (V1) and antidiuretic (V2) effects of vasopressin on progression. Male homozygous Brattleboro rats with hereditary central diabetes insipidus were submitted to 5/6 nephrectomy. They were divided into three groups, two of which received chronic i.p. infusion of AVP (V1 + V2 effects) or dDAVP (V2 effects). The third group served as control (CONT). The doses of AVP and dDAVP were chosen so as to produce urine osmolality similar to that observed in 5/6 Nx Sprague Dawley rats. All rats ate the same amount of food and drank water ad libitum. Renal function was studied for 13 weeks. All three groups showed a marked hypertension. Rats infused with dDAVP, but not those infused with AVP, had a higher creatininemia, anemia and urinary protein excretion than CONT rats. In the dDAVP but not the AVP group, fractional excretion of urea was markedly decreased and plasma urea concentration rose much more than that of creatinine. These results show that V2 but not V1 effects play a major role in the deleterious influence of vasopressin on progression, at least in Brattleboro rats. The more severe progression seen in dDAVP rats could indirectly result from the V2-mediated effects on the collecting duct resulting in a decreased efficiency of urea excretion, an increased intrarenal urea recycling, and a rise in plasma urea concentration. Both the toxic effects of urea and the recently demonstrated V2-mediated increase in glomerular hemodynamics might be involved in the deleterious influence of V2 agonism.
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PMID:Contribution of vasopressin to progression of chronic renal failure: study in Brattleboro rats. 1049 67

Aquaporin-2 (AQP-2), a water channel located on the apical membrane of collecting duct cells, regulates water reabsorption under the control of vasopressin (AVP). Using an antibody directed to human AQP-2, a quantitative Western blot analysis was performed to determine the collecting duct responsiveness to an oral, nonpeptide, V2 receptor antagonist (VPA-985) in patients with chronic NYHA II and III heart failure. Standards were derived by conjugating the immunizing peptide to maleimide-activated bovine serum albumin and a standard curve was generated for each blot. Quantification of baseline steady-state AQP-2 excretion was done by collecting urine on the day before study drug administration. The next day patients received either placebo or VPA-985 at one of four different doses and urine was collected every 2 h. Thereafter, urinary AQP-2 excretion was calculated as a ratio of the urine flow and was expressed in pmol/h. During baseline, steady-state excretion did not change significantly (T0-T2, 458 +/- 44; T2-T4, 443 +/- 35; T4-T6, 422 +/- 35; T6-T8, 401 +/- 30). Compared to placebo, urinary AQP-2 excretion decreased significantly and in all groups in a dose-dependent manner during VPA-985 administration. The most impressive decrease was observed in the 250-mg group (T0-T2, 89 +/- 5; T2-T4, 50 +/- 18; T4-T6, 43 +/- 22; T6-T8, 42 +/- 23; P < 0.001 during each period compared with baseline and placebo results). VPA-985 significantly increased solute-free water clearance and urine output and significantly decreased urinary osmolality. Urinary AQP-2 excretion correlated best with solute-free water clearance during T0-T2 and T2-T4 collection, but a correlation with urinary osmolality and urinary output was also found during these periods. In conclusion, AQP-2 urinary excretion, as measured by quantitative Western analysis, is a sensitive biologic marker to assess the short-term responsiveness of the collecting duct to a V2 receptor AVP antagonist in chronic heart failure.
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PMID:Selective V2-receptor vasopressin antagonism decreases urinary aquaporin-2 excretion in patients with chronic heart failure. 1050 93


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