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)

In cultured renal cells, hypertonicity activates multiple mitogen-activated protein kinases (MAPKs) and enhances the expression of heat shock proteins (HSPs). In rats, 24 h water restriction increased mean urinary osmolality (Uosm) from 2, 179+/-153 mOsm/kg to 2,944+/-294 mOsm/kg (P < 0.001) and was associated with significant (P < 0.05) increases in the papillary activity of c-Jun NH2-terminal protein kinase (JNK) by 22%, extracellular signal-regulated protein kinase (ERK) by 49%, and p38 MAPK by 15%. Conversely, 24 h of water-loading (Uosm 473+/-33 mOsm/kg) caused suppression of JNK activity by 43% (P < 0.001), ERK by 39% (P < 0.05), and p38 MAPK by 26% (P < 0.05). No such modulation was observed in the isotonic cortex. c-Jun phosphorylation was decreased in papilla from water-loaded rats by 45% versus controls. Expression of Hsp 110, inducible Hsp 70, and Hsp 25 was greater in the hyperosmotic papilla than the isosmotic cortex but was not affected by the animal's hydration state. In cultured inner medullary collecting duct cells, HSP expression was maximal at 500 mOsm/kg, while activation of JNK continued to increase. We conclude that under basal conditions of hydration, these HSPs are maximally expressed in the hypertonic inner medulla, while the activation of all three members of the MAPK family approaches but is not maximal.
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PMID:In vivo regulation of MAP kinases in Ratus norvegicus renal papilla by water loading and restriction. 981 74

Aquaporin-2 (AQP2), the protein that mediates arginine vasopressin (AVP)-regulated apical water transport in the renal collecting duct, possesses a single consensus phosphorylation site for cAMP-dependent protein kinase A (PKA) at Ser256. The aim of this study was to examine whether AVP, and other agents that increase cAMP levels, could stimulate the phosphorylation of AQP2 in intact rat renal tissue. Rat renal papillae were prelabeled with 32P and incubated with vehicle or drugs, and then AQP2 was immunoprecipitated. Two polypeptides corresponding to nonglycosylated (29 kDa) and glycosylated (35-48 kDa) AQP2 were identified by SDS-PAGE. AVP caused a time- and dose-dependent increase in phosphorylation of both glycosylated and nonglycosylated AQP2. The threshold dose for a significant increase in phosphorylation was 10 pM, which corresponds to a physiological serum concentration of AVP. Maximal phosphorylation was reached within 1 min of AVP incubation. This effect on AQP2 phosphorylation was mimicked by the vasopressin (V2) agonist, 1-desamino-[8-D-arginine]vasopressin (DDAVP), or forskolin. Two-dimensional phosphopeptide mapping indicated that AVP and forskolin stimulated the phosphorylation of the same site in AQP2. Immunoblot analysis using a phosphorylation state-specific antiserum revealed an increase in phosphorylation of Ser256 after incubation of papillae with AVP. The results indicate that AVP stimulates phosphorylation of AQP2 at Ser256 via activation of PKA, supporting the idea that this is one of the first steps leading to increased water permeability in collecting duct cells.
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PMID:Arginine vasopressin stimulates phosphorylation of aquaporin-2 in rat renal tissue. 995 Sep 56

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

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

cAMP mediates many of the effects of vasopressin, prostaglandin E2, and beta-adrenergic agents upon salt and water transport in the renal collecting duct. The present studies examined the role of cAMP-dependent protein kinase (PKA) in mediating these effects. PKA is a heterotetramer comprised of two regulatory (R) subunits and two catalytic (C) subunits. The four PKA isoforms may be distinguished by their R subunits that have been designated RIalpha, RIbeta, RIIalpha, and RIIbeta. Three regulatory subunits, RIalpha, RIIalpha, and RIIbeta, were detected by immunoblot and ribonuclease protection in both primary cultures and fresh isolates of rabbit cortical collecting ducts (CCDs). Monolayers of cultured CCDs grown on semipermeable supports were mounted in an Ussing chamber, and combinations of cAMP analogs that selectively activate PKA type I vs. PKA type II were tested for their effect on electrogenic ion transport. Short-circuit current (Isc) was significantly increased by the PKA type II-selective analog pairs N6-monobutyryl-cAMP plus 8-(4-chlorophenylthio)-cAMP or N6-monobutyryl-cAMP plus 8-chloro-cAMP. In contrast the PKA type I-selective cAMP analog pair [N6-monobutyryl-cAMP plus 8-(6-aminohexyl)-amino-cAMP] had no effect on Isc. These results suggest PKA type II is the major isozyme regulating electrogenic ion transport in the rabbit collecting duct.
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PMID:Type II cAMP-dependent protein kinase regulates electrogenic ion transport in rabbit collecting duct. 1019 23

The early phase of the stimulatory effect of aldosterone on sodium reabsorption in renal epithelia is thought to involve activation of apical sodium channels. However, the genes initiating this effect are unknown. We used a combination of polymerase chain reaction-based subtractive hybridization and differential display techniques to identify aldosterone-regulated immediate early genes in renal mineralocorticoid target cells. We report here that aldosterone rapidly increases mRNA levels of a putative Ser/Thr kinase, sgk (or serum- and glucocorticoid-regulated kinase), in its native target cells, i.e. in cortical collecting duct cells. The effect occurs within 30 min of the addition of aldosterone, is mediated through mineralocorticoid receptors, and does not require de novo protein synthesis. The full-length sequences of rabbit and mouse sgk cDNAs were determined. Both cDNAs show significant homology to rat and human sgk (88-94% at the nucleotide level, and 96-99% at the amino acid level). Coexpression of the mouse sgk in Xenopus oocytes with the three subunits of the epithelial Na+ channel results in a significantly enhanced Na+ current. These results suggest that sgk is an immediate early aldosterone-induced gene, and this protein kinase plays an important role in the early phase of aldosterone-stimulated Na+ transport.
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PMID:sgk is an aldosterone-induced kinase in the renal collecting duct. Effects on epithelial na+ channels. 1035 46

The ROMK channel plays an important role in K recycling in the thick ascending limb (TAL) and K secretion in the cortical collecting duct (CCD). A large body of evidence indicates that the ROMK channel is a key component of the native K secretory channel identified in the apical membrane of the TAL and the CCD. Although the ROMK channel shares several key regulatory mechanisms with the native K secretory channel in a variety of respects, differences in the channel modulatory mechanism are clearly present between the ROMK channel and the native K secretory channel. Therefore, it is possible that additional associate proteins are required to interact with the ROMK channel to assemble the native K secretory channel. This notion is supported by recent reports showing that cystic fibrosis transmembrane conductance regulator (CFTR) and A kinase anchoring proteins (AKAP) interact with the ROMK channels to restore the response to ATP sensitivity and protein kinase A stimulation. This review is an attempt to summarize the up-to-date progress regarding the interaction between the ROMK channel and the associate proteins in forming the native K secretory channel.
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PMID:Regulation of the ROMK channel: interaction of the ROMK with associate proteins. 1060 Sep 28

Phosphorylation of Ser(256), in a PKA consensus site, in AQP2 (p-AQP2) appears to be critically involved in the vasopressin-induced trafficking of AQP2. In the present study, affinity-purified antibodies that selectively recognize AQP2 phosphorylated at Ser(256) were developed. These antibodies were used to determine 1) the subcellular localization of p-AQP2 in rat kidney and 2) changes in distribution and/or levels of p-AQP2 in response to [desamino-Cys(1),D-Arg(8)]vasopressin (DDAVP) treatment or V(2)-receptor blockade. Immunoelectron microscopy revealed that p-AQP2 was localized in both the apical plasma membrane and in intracellular vesicles of collecting duct principal cells. Treatment of rats with V(2)-receptor antagonist for 30 min resulted in almost complete disappearance of p-AQP2 labeling of the apical plasma membrane with only marginal labeling of intracellular vesicles remaining. Immunoblotting confirmed a marked decrease in p-AQP2 levels. In control Brattleboro rats (BB), lacking vasopressin secretion, p-AQP2 labeling was almost exclusively present in intracellular vesicles. Treatment of BB rats with DDAVP for 2 h induced a 10-fold increase in p-AQP2 labeling of the apical plasma membrane. The overall abundance of p-AQP2, however, was not increased, as determined both by immunoelectron microscopy and immunoblotting. Consistent with this, 2 h of DDAVP treatment of normal rats also resulted in unchanged p-AQP2 levels. Thus the results demonstrate that AQP2 phosphorylated in Ser(256) is present in the apical plasma membrane and in intracellular vesicles and that both the intracellular distribution/trafficking, as well as the abundance of p-AQP2, are regulated via V(2) receptors by altering phosphorylation and/or dephosphorylation of Ser(256) in AQP2.
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PMID:Localization and regulation of PKA-phosphorylated AQP2 in response to V(2)-receptor agonist/antagonist treatment. 1064 53

Prostaglandin E(2) (PGE(2)) antagonizes the action of arginine vasopressin (AVP) on collecting duct water permeability. To investigate the mechanism of this antagonism, rat renal inner medulla (IM) was incubated with the two hormones, and the phosphorylation and subcellular distribution of the water channel, aquaporin-2 (AQP2) were studied. Using a phosphorylation state-specific AQP2 antibody, we demonstrated that AVP stimulates AQP2 phosphorylation at the Ser(256) protein kinase A consensus site in a time- and dose-dependent manner. In parallel studies using a differential centrifugation technique, we demonstrated that AVP induced translocation of AQP2 from an intracellular vesicle-enriched fraction to a plasma membrane-enriched fraction. PGE(2) (10(-7) M) added after AVP (10(-8) M) did not decrease AQP2 phosphorylation but reversed AVP-induced translocation of AQP2 to the plasma membrane. Preincubation of IM with PGE(2) did not prevent the effects of AVP on AQP2 phosphorylation and trafficking. PGE(2) alone did not influence AQP2 phosphorylation and subcellular distribution. Our data indicate that 1) recruitment of AQP2 to the plasma membrane and its retrieval to a pool of intracellular vesicles may be regulated independently, 2) PGE(2) may counteract AVP action by activation of AQP2 retrieval, 3) dephosphorylation of AQP2 is not a prerequisite for its internalization.
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PMID:Prostaglandin E(2) interaction with AVP: effects on AQP2 phosphorylation and distribution. 1071 May 43

The sgk, an aldosterone-induced gene in mineralocorticoid target cells, regulates the epithelial sodium channel. Aldosterone increases sodium reabsorption in tight epithelia. The early phase of this stimulatory effect is thought to involve activation of apical sodium channels. To identify immediate-early genes that initiate this effect, we used a combination of polymerase chain reaction-based subtractive hybridization and differential display techniques. This review summarizes our recent findings. Aldosterone rapidly increases mRNA levels of a putative Ser/Thr kinase, sgk (or serum- and glucocorticoid-regulated kinase), in the native mineralocorticoid target cells, that is, in cortical collecting duct (CCD) cells. The induction of sgk mRNA occurs within 30 minutes of the addition of aldosterone and does not require de novo protein synthesis, indicating that sgk is an immediate/early aldosterone-induced gene. Induction of sgk by aldosterone is mediated through mineralocorticoid receptors (MRs), since it is prevented by ZK91857, an MR antagonist, but not by RU486, a glucocorticoid antagonist. In addition to aldosterone, RU28362, a pure glucocorticoid receptor agonist, also induced sgk mRNA, both in primary cultures of rabbit CCD cells and in the M-1 mouse CCD cell line. Sgk mRNA levels are also influenced by changes in the osmolality of the medium. In M-1 cells, incubation of cells for one hour in a mildly hypotonic medium decreased sgk mRNA levels, whereas incubation in hypertonic medium brought about opposite changes. To determine whether sgk is involved in the regulation of the epithelial sodium channel (ENaC), we coexpressed the full-length sgk cRNA in Xenopus oocytes with the three ENaC subunits. Expression of sgk resulted in a significant increase in the amiloride-sensitive Na current, suggesting that this protein kinase plays an important role in the early phase of aldosterone-stimulated Na transport. These results indicate that sgk is an aldosterone-induced immediate/early gene in native MR target cells, and is involved in the regulation of ion transport and possibly cell volume.
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PMID:The sgk, an aldosterone-induced gene in mineralocorticoid target cells, regulates the epithelial sodium channel. 1076 56


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