UNIPROT:P41181 - FACTA Search

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Query: UNIPROT:P41181 (collecting duct)
5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we demonstrated that the mIMCD-K2 cell line, derived from the inner medullary collecting duct (IMCD) of a transgenic mouse, secretes Cl- by an electrogenic mechanism [N. L. Kizer, B. Lewis, and B. A. Stanton, Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995]. The objective of the present study was to characterize the cellular mechanisms of electrogenic Cl- secretion (IscCl) and to determine whether arginine vasopressin (AVP) and adenosine 3',5'-cyclic monophosphate (cAMP) stimulate IscCl. To this end, we measured IscCl across monolayers of mIMCD-K2 cells mounted in Ussing-type chambers. AVP increased IscCl with a Michaelis constant (Km) of 2.1 +/- 0.7 x 10(-12) M. 1-Desamino-8-D-AVP, a specific V2 receptor agonist, increased IscCl from 3.3 +/- 0.4 to 17.4 +/- 1.3 microA/cm2, 8-(4-Chlorophenylthio)-cAMP, a cell-permanent analogue of cAMP, a second messenger of AVP, increased IscCl from 1.4 +/- 0.3 to 15.2 +/- 1.2 microA/cm2. Furosemide and bumetanide, inhibitors of Na(+)-2Cl(-)-K+ cotransport, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of Cl-/HCO3- exchange, reduced IscCl when added to the basolateral solution. Our data suggest that AVP, via V2 receptors, and the second messenger cAMP stimulate IscCl and that Cl- secretion by mIMCD-K2 cells involves uptake of Cl- across the basolateral membrane by Na(+)-2Cl(-)-K+ cotransport and Cl-/HCO3- exchange and diffusion out of the cells across the apical membrane by cystic fibrosis transmembrane conductance regulator Cl- channels.
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PMID:Vasopressin and cAMP stimulate electrogenic chloride secretion in an IMCD cell line. 777 14

To clarify the mechanism of action of arginine vasopressin (AVP) on ionic conductances, electrophysiological technique was applied to the rabbit cortical collecting duct (CCD) perfused in vitro. When AVP (100 pM) was added to the bath, transepithelial voltage (VT), transepithelial resistance (RT), and fractional resistance of the apical membrane (fRA) of the principal cell displayed biphasic responses: initial increase in lumen-negative VT (phase I) was associated with decreases in RT and fRA, whereas secondary decrease in VT (phase II) was associated with increases in RT and fRA. In phase I, depolarization of the luminal membrane was observed due to stimulation of Na+ conductance in the luminal membrane. In phase II, mixed responses of both hyperpolarization of the luminal membrane, due to late inhibition of Na+ conductance, and depolarization of the basolateral membrane, due to stimulation of Cl- conductance, were observed. 8-(4-Chlorophenylthio)-adenosine 3',5'-cyclic monophosphate, as a pure vascular AVP receptor 2 (V2) action, mimicked the actions of AVP. Addition of AVP (100 pM to 1 nM) in the lumen resulted in increases in lumen-negative VT and RT. Luminal AVP did not affect the electrical parameters in beta-intercalated cells. In principal cells, luminal AVP caused sustained increase in total membrane resistance (Ri), together with an initial depolarization of the luminal membrane followed by a late hyperpolarization of the basolateral membrane. Because the initial response was abolished in the presence of 2 mM Ba2+ in the lumen, an inhibition of luminal K+ conductance may be responsible for the initial phase of luminal AVP action. Late hyperpolarization of the basolateral membrane associated with an increase in membrane resistance was abolished in the absence of ambient Cl-. Under the condition where Cl- conductance of the basolateral membrane was stimulated by administration of cAMP in the bath, voltage deflections of the basolateral membrane on changing Cl- concentration in the bath from 120 to 12 mM decreased by 88% in the presence of luminal AVP. These observations are in accord with the view that the basolateral Cl- conductance was inhibited by luminal AVP in the later phase. These data indicate that AVP in the lumen inhibits basolateral Cl- conductance, which is stimulated by AVP in the bath.
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PMID:Electrophysiological study of luminal and basolateral vasopressin in rabbit cortical collecting duct. 784 Feb 44

Prolonged fluid restriction in rats is accompanied by functional modifications of the terminal part of the inner medullary collecting duct (IMCD) revealed by a sustained increase in arginine vasopressin (AVP)-independent transepithelial osmotic water permeability (PTE) in vitro. The cellular basis of this adaptation was explored in isolated and perfused terminal IMCDs of Sprague-Dawley rats using video and fluorescence microscopy. Basolateral membrane osmotic water permeability (Posm), transcellular Posm, and PTE were measured in quick sequence in every tubule. They were expressed per unit area of basolateral membrane corrected for infoldings, based on previous stereological studies and assuming no major change in membrane surface area between hydrated and dehydrated animals. Compared with IMCDs of rats with a high water intake, IMCDs of rats deprived of fluid for 36 h displayed a significantly higher basal PTE (24.9 +/- 5.1 vs. 6.1 +/- 0.6 microns/s), a similar basolateral Posm, and a higher transcellular Posm, implying a higher permeability of the apical membrane, despite the absence of exogenous AVP. However, when IMCDs of thirsted rats were exposed to AVP in vitro, their transcellular Posm (36.0 +/- 2.4 microns/s) was significantly smaller than their PTE determined simultaneously (51.8 +/- 7.1 microns/s), suggesting that part of the water flow may follow a paracellular route. A change in paracellular pathways was supported by higher apparent permeabilities to [14C]sucrose (0.85 +/- 0.27 vs. 0.28 +/- 0.04 x 10(-5) cm/s) and to [methoxy-3H]inulin (0.25 +/- 0.04 vs. 0.14 +/- 0.03 x 10(-5) cm/s) in IMCDs of thirsted rats. The nonelectrolyte permeabilities were affected neither by AVP nor by urea-rich bathing solutions. We conclude that in vivo factors related to dehydration produce a conditioning effect on terminal IMCD, which includes stabilization of the apical membrane in a state of high Posm and opening up of paracellular pathways revealed by a higher permeability to water and nonelectrolytes. The role of these adaptive phenomena remains unclear but may pertain to the sudden transitions between antidiuresis and diuresis.
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PMID:Adaptation of inner medullary collecting duct to dehydration involves a paracellular pathway. 784 Feb 48

Endothelin is an important modulator of renal function via its binding to abundant receptors in renal tissue and by the ability of renal endothelial and epithelial cells to synthesize and release endothelin. In the kidney, endothelin may function as a paracrine-autocrine factor in the regulation of renal blood flow, glomerular hemodynamics, and sodium and water homeostasis. Recent evidence suggests that circulating endothelin may play an important role in renal regulation in cardiorenal states of endothelin activation. Endothelin is a potent renal vasconstrictor that has dual actions on glomerular filtration rate due to its ability to preferentially constrict efferent arterioles preserving glomerular filtration. Furthermore, endothelin modulates sodium excretion and water balance at the level of the proximal tubule and medullary collecting ducts, respectively, by mechanisms that are still unclear. In addition, endothelin stimulates the renin-angiotensin-aldosterone system and atrial natriuretic peptide release and inhibits arginine vasopressin-mediated water reabsorption in the inner medullary collecting duct. Recent studies using specific receptor antagonists have demonstrated a pathophysiologic role for endothelin during renal ischemia, cyclosporine-induced toxicity, and chronic renal failure. This review highlights recent research that supports an important role for endothelin as a locally produced vasoactive and natriuretic peptide in the regulation of renal hemodynamic and excretory functions.
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PMID:Physiologic and pathophysiologic roles of endothelin in the kidney. 785 Apr 14

Studies were conducted to determine whether the cortical collecting duct (CCD) of the Dahl salt-resistant rat (inbred Rapp strain; R/Jr) exhibits the same responses to deoxycorticosterone (DOC; 2.5 mg as a depot injection in vivo, 3-8 days before experimentation) and arginine vasopressin (AVP, 220 pM in vitro) as the Sprague-Dawley (SD) [L. Chen, S.K. Williams, and J.A. Schafer. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28): F147-F156, 1990] and Dahl salt-sensitive (inbred Rapp strain, S/Jr) [C.T. Hawk and J.A. Schafer. Am. J. Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F471-F478, 1991] CCD. Qualitatively, the R/Jr CCD responded as in the other two strains: AVP elevated the osmotic water permeability (Pf, micron/s) from 0 to approximately 1,200; either AVP or DOC, when used alone, increased the lumen-to-bath 22Na+ flux (Jl-->b, pmol.min-1.mm-1) from the control range of 20-25 to approximately 40 and hyperpolarized the transepithelial voltage. AVP and DOC effects were synergistic, elevating Jl-->b to 90 +/- 5 (mean +/- SE) with both hormones, but this value was significantly lower than observed previously in both the SD and the S/Jr CCD, 125 +/- 6 and 140 +/- 6, respectively. However, bath-to-lumen fluxes (Jb--l) were also significantly lower than observed in the SD and S/Jr CCD. Because net fluxes (Jnet) in these experiments can be determined only as nonpaired differences between unidirectional fluxes, it is uncertain whether Jnet values in the R/Jr CCD are significantly lower than in the SD or S/Jr CCD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sodium and water transport in cortical collecting duct of Dahl salt-resistant rat. 794 56

1. Chronic adrenal insufficiency impairs maximal urine concentration, probably in part due to reduced medullary tonicity but also possibly by inhibition of distal nephron water transport. This latter defect has been demonstrated in rabbit but not in rat. 2. Since the time between adrenalectomy and experiment was different in rabbit and rat studies, diffusional water permeability was evaluated in the papillary collecting duct in the absence and presence of submaximal (20 microU/mL) and supramaximal (200 microU/mL) arginine vasopressin (AVP) in adrenalectomized rats at 7, 14 and 21 days. 3. Experimentation 7 days after adrenalectomy failed to demonstrate significantly altered basal or AVP-induced water permeability which increased by 23 and 78% with submaximal and supramaximal concentrations, respectively. Submaximal AVP concentrations also induced a comparable change in water permeability in adrenalectomized rats at 14 days; however, 21 days after adrenalectomy, diffusional water permeability was not increased by 20 microU/mL AVP (3.31 +/- 0.22 to 3.31 +/- 0.24 microns/s). Nevertheless, the effect of a supramaximal AVP concentration (200 microU/mL) was not altered by adrenalectomy (4.54 +/- 0.39 to 8.08 +/- 0.96; P < 0.01). Incubation of collecting ducts in aldosterone for 2 h did not reverse the inhibitory effect of chronic adrenalectomy on AVP-stimulated water transport. 4. These studies suggest that mineralocorticoid withdrawal does impair the hydro-osmotic action of AVP in the rat papillary collecting duct but that this effect takes between 14 and 21 days to occur.
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PMID:The effect of adrenalectomy on water permeability in rat papillary collecting duct. 795 47

In rabbit cortical collecting duct (CCD) cells, arginine vasopressin (AVP) causes a transient increase followed by a sustained depression of transepithelial potential difference (PDte). Mechanisms underlying the decrease in PDte are not well understood. In this study, we used primary cultures of rabbit CCD cells to study effects of AVP. Basolateral addition of AVP caused a dose-dependent increase in transepithelial conductance (Gte) and a corresponding decrease in PDte. A significant effect was observed at 1 pM AVP, and half-maximal response occurred at 30 pM AVP; 1 nM AVP increased Gte and decreased PDte. Replacement of apical Na+ with N-methyl-D-glucamine did not prevent the effect of AVP on Gte, suggesting that it is not mediated by an increase in apical Na+ conductance. Similarly, apical Ba2+ (1 mM) or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 0.1 mM) failed to prevent the effect of AVP. On the other hand, 5-nitro-2(3-phenylpropylamino)benzoic acid (0.1 mM) caused partial inhibition, whereas substitution of apical Cl- with gluconate or cyclamate almost completely prevented the AVP-induced increase in Gte. In unidirectional ion-flux studies, 1 nM AVP caused only a modest increase in apical-to-basolateral (A-->BL) flux of 22Na and had no effect on transepithelial flux of 86Rb in either direction. On the other hand, AVP caused a pronounced increase in A-->BL flux and BL-->A flux of 36Cl, resulting in an increased net Cl- absorption. The effect of AVP on Gte could be mimicked by 8-bromo-adenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) and isoproterenol, and effects of AVP and isoproterenol were not additive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasopressin activates a chloride conductance in cultured cortical collecting duct cells. 797 87

Congenital nephrogenic diabetes insipidus (CNDI) is a rare X-linked disorder in which the renal collecting duct is unresponsive to arginine vasopressin, and thus, the urine is consistently hypotonic to plasma. As a result, affected individuals are unable to concentrate urine and suffer from episodes of severe dehydration and hypernatremia. Recently, the association between arginine vasopressin V2 receptor gene mutations and CNDI has been demonstrated. In this report, two additional novel molecular defects of the arginine vasopressin V2 receptor gene in CNDI families are described. In one family, the affected individual demonstrated a G-->T transversion causing a nonsense mutation in codon 231. This mutation results in a glutamic acid becoming a termination codon, causing premature termination and truncation of the encoded receptor protein. This mutation causes a NciI site within the gene to be abolished and a BsaWI site to be created. In the second family, affected individuals showed a 28-basepair duplicating insertion in the very beginning of exon 2 down-stream of the splice acceptor site. It was hypothesized that an insertion mutagenesis mechanism involves the formation of a stem-loop structure within the newly synthesized DNA strand, followed by a slipped mispairing. This may be a general mechanism for the deletion or insertion of repeated sequences within the genome. Recent data show that G-protein-coupled receptors are susceptible to many different mutations that often result in the loss of function, causing a similar clinical phenotype.
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PMID:Mutations in the vasopressin V2 receptor gene in two families with nephrogenic diabetes insipidus. 799 96

The immature kidney is characterized by resistance to arginine vasopressin (AVP). In the immature cortical collecting duct (iCCD), AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation is decreased, but the mechanisms involved are not known. We examined cAMP production in isolated CCD from immature and mature rabbits. Cellular cAMP levels were measured by radioimmunoassay under basal conditions and after stimulation with hormone. Basal cAMP production in the iCCD was not different from that in the mature CCD (mCCD). In contrast, AVP- and forskolin-stimulated cAMP generation were severely decreased in the iCCD. Inhibition of endogenous prostaglandin production by indomethacin increased AVP-stimulated cAMP generation in the iCCD to levels that were not different from the mCCD. Inhibition of protein kinase C (PKC) by staurosporine and inhibition of Gi by pertussis toxin elicited a mature cAMP response in the iCCD. These data suggest that the defect in AVP-stimulated cAMP production in the iCCD is mediated by prostaglandins via 1) activation of Gi and 2) direct inhibition of the adenylyl cyclase catalytic subunit. In addition, PKC appears to play a significant role.
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PMID:Prostaglandins mediate the defect in AVP-stimulated cAMP generation in immature collecting duct. 804 63

The urinary bladder of the aquatic toad Xenopus laevis is known to exhibit a low permeability to water and a poor sensitivity to antidiuretic hormone. In order to precise the characteristics and the specific cellular mechanisms of this reduced hydro-osmotic response we used a sensitive volumetric technique to monitor net water flow and studied the correlation between the antidiuretic hormone (ADH)-induced net water flow and the fine ultrastructural appearance of the urinary bladder epithelium. Transmural net water flow was entirely dependent on the osmotic gradient across the preparation and not on the hydrostatic pressure difference. We observed the existence of a low but significant hydro-osmotic response to arginine vasopressin. Freeze-fracture electron microscopy demonstrated the presence of typical aggrephores in the subapical cytoplasm. The response to the hormone was accompanied by the appearance of typical intramembrane aggregates into the apical plasma membrane. Water permeability increase and apical aggregate insertion were both slowly but fully reversible. Except for the multilayered structure of the epithelium and the particularly low response to antidiuretic hormone, all the studied permeability and ultrastructural characteristics of the bladder were thus very similar to those observed in other sensitive epithelia such as the amphibian bladder and skin and the mammalian collecting duct which exhibit a high hydro-osmotic response to the hormone.
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PMID:Antidiuretic response in the urinary bladder of Xenopus laevis: presence of typical aggrephores and apical aggregates. 805 83

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