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)

We established renal cell lines from definite nephron segments which were microdissected from kidneys of transgenic C57BL/6 mice, harboring the large T-antigen gene of temperature-sensitive mutant simian virus 40, pSVtsA58(ori-). Cell culture was under a humidified atmosphere of 5% CO2 in air, on collagen-coated dishes, and in RITC80-7 medium with 5% fetal bovine serum, 10 micrograms/ml transferrin, 1 microgram/ml insulin, 10 ng/ml recombinant human EGF, penicillin and streptomycin. Cell line which kept contact inhibition character was established from each segment. Cells derived from distal tubule, cortical and outer medullary collecting duct possessed their cyclic AMP response to arginine-vasopressin, like their original nephron segment. On the other hand, cells derived from terminal proximal tubules (S3 segment) formed a cobblestone-like confluent monolayer, and did not respond to arginine-vasopressin like their fresh segments. Since cisplatin, a well-known nephrotoxic substance, damages proximal tubules (especially S3) rather than collecting ducts, we assayed cell number, protein content, and ATP content of cultured S3 cells at various times after addition of 0.2 mM cisplatin. Decrease of cell number, total protein content and total ATP content of culture cells occurred after 10 h incubation with 0.2 mM cisplatin. The 50% lethal dose (LD50) of cisplatin in S3 cells was 4 x 10(-5) M after 20 h incubation and 8.5 x 10(-6) M after 40 h incubation. Outer medullary collecting duct (OMCD) cells were damaged 30% maximally after 20 h incubation with cisplatin, and LD50 in them became 2.5 x 10(-5) M after 40 h incubation. We could show that the LD50 of cisplatin in the OMCD cell line was three times higher than that in the S3 cell line. Thus, these cell lines are the first in the kidney to definite the segmental origin and to maintain some differentiated unique functions. They are valuable for studies on intrarenal site-specific actions and possible mechanisms of action of pharmacological and toxic substances.
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PMID:Cisplatin-induced toxicity in immortalized renal cell lines established from transgenic mice harboring temperature sensitive SV40 large T-antigen gene. 885 99

The divalent mineral cations Ca2+ and Mg2+ play many and diverse roles both in the function of cells and in extracellular processes. The metabolism of these cations is a complex process involving the coordinated function of several organ systems and endocrine glands. A recently cloned G-protein-coupled receptor responds to extracellular calcium concentration (Ca2+0-sensing receptor, CaSR) and mediates several of the known effects of Ca2+0 on parathyroid and renal function. The CaSR, which is also expressed in a number of other tissues including thyroidal C-cells, brain and gastrointestinal tract, may function as a Ca2+0 sensor in these tissues as well. Thus, Ca2+0 is a first messenger (or hormone) which, via CaSR-mediated activation of second messenger systems (e.g. phospholipases C and A2, cyclic AMP) leads to altered function of these cells. Several mutations in the human CaSR gene have been identified and shown to cause three inherited diseases of calcium homeostasis, clearly implicating the CaSR as an important component of the homeostatic mechanism for divalent mineral ions. Ca2+ and Mg2+ losses from the body are regulated by altering the urinary excretion of these divalent cations. The localization of the CaSR transcripts and protein in the kidney not only provides a basis for a direct Ca2+0 (or Mg2+0)-mediated regulation of Ca2+ (and Mg2+) excretion but also suggests a functional link between divalent mineral and water metabolism. In the kidney, the thick ascending limb of Henle (TAL) plays crucial roles in regulating both divalent mineral reabsorption and urine concentration. Recent studies have suggested models whereby extracellular Ca2+, via the CaSR expressed in the TAL as well as in the collecting duct system, modulates both Ca2+ 0 and Mg2+ 0 as well as water reabsorbtion. When taken together, these studies suggest that the CaSR not only provides the primary mechanism for Ca2+ 0-mediated regulation of parathyroid hormone secretion from parathyroid glands but also for direct modulation of renal divalent mineral excretion and urinary concentrating ability. These latter functions may furnish a mechanism for integrating and balancing water and divalent cation losses that minimizes the risk of urinary tract stone formation. This mechanism can explain hypercalcemia-mediated polyuria (diabetes insipidus).
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PMID:Role of the Ca(2+)-sensing receptor in divalent mineral ion homeostasis. 905 Feb 37

Using a laser scanning confocal microscopy of fluorescent Ca2+ indicator (Fluo-3-AM) the spatiotemporal Ca2+ dynamics in cultured kidney inner medullary collecting duct cells was investigated. In response to extracellular ATP (100 microM), nuclear (Fln) and cytosolic (Flc) fluorescence intensity increased simultaneously. UTP similarly increased Fln and Flc, but ADP and AMP did not. A ratio between Fln and Flc was about 1.06 +/- 0.03 at rest and increased 1.71 +/- 0.02 at the peak of stimulation (n = 74). In Ca(2+)-free condition, ATP increased Fln and Flc with a smaller peak intensity, but the peak ratio was similar (1.52 +/- 0.03, n = 70). Faster time resolution of 100 ms in line scanning mode did not detect the delay between nuclear and cytosolic Ca2- responses. Our results indicate that nuclear Ca2+ was not diffused from the cytoplasm and that it may be directly released from the nuclear envelope, a possible Ca2+ store.
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PMID:Nuclear and cytosolic calcium signaling induced by extracellular ATP in rat kidney inner medullary collecting duct cells. 916 93

Vasopressin regulates water excretion from the kidney by increasing the osmotic water permeability of the renal collecting duct. The aquaporin-2 water channel has been demonstrated to be the target for this action of vasopressin. Recent studies have demonstrated that vasopressin, acting through cyclic AMP, triggers fusion of aquaporin-2-bearing vesicles with the apical plasma membrane of the collecting duct principal cells. The vesicle-targeting proteins synaptobrevin-2 and syntaxin-4 are proposed to play roles in this process.
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PMID:Regulation of aquaporin-2 water channel trafficking by vasopressin. 926 Oct 56

1. The aim of the present study was to investigate the transduction pathways elicited by prostaglandin E2 (PGE2) to inhibit hormone-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in the outer medullary collecting duct (OMCD) and medullary thick ascending limb (MTAL) microdissected from the rat nephron. 2. In the OMCD, 0.3 microM PGE2 and low concentrations of Ca2+ ionophores (10 nM ionomycin or 50 nM A23187) inhibited by about 50% a same pool of arginine vasopressin (AVP)-stimulated cyclic AMP content through a same process insensitive to Bordetella pertussis toxin (PTX). 3. Sulprostone, an agonist of the EP1/EP3 subtypes of the PGE2 receptor, decreased AVP-dependent cyclic AMP accumulation in OMCD and MTAL samples. The concentration eliciting half-maximal inhibition was of about 50 nM in OMCD and 0.1 nM in MTAL. 4. In MTAL, 1 nM sulprostone and PGE2 inhibited by about 90% a same pool of AVP-dependent cyclic AMP content through a PTX-sensitive, Ca2+ -independent pathway. 5. In the OMCD, PGE2 decreased by about 50% glucagon-dependent cyclic AMP synthesis by a process sensitive to PTX and Ca2+ -independent. Sulprostone 1 nM induced the same level of inhibition. 6. These results demonstrate that PGE2 decrease hormone-dependent cyclic AMP accumulation through a G(alpha)i-mediated inhibition of adenylyl cyclase activity in MTAL cells and glucagon-sensitive cells of the OMCD or through a PTX-insensitive increase of intracellular Ca2+ concentration in AVP-sensitive cells of the OMCD.
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PMID:Cell-specific coupling of PGE2 to different transduction pathways in arginine vasopressin- and glucagon-sensitive segments of the rat renal tubule. 1019 86

AVP not only increases osmotic water permeability (Pf) in the rat cortical collecting duct (CCD), but also acts synergistically with aldosterone to augment sodium reabsorption (JNa). These effects are inhibited by catecholamines via alpha2 adrenergic receptors, and by dopamine. We review here studies designed to determine the mechanism and receptor involved in dopamine action. The inhibitory effect of dopamine on Na+ and water transport was found to be reversible, and was not produced by agonists specific to D1A and D1B receptors. D2-type (D2, D3 or D4) receptors and activation of the GTP-binding protein Gi were implicated by the observation that dopamine had no inhibitory effect when JNa and Pf were stimulated by a cyclic AMP analogue plus isobutylmethylxanthine. The only dopaminergic antagonist that reversed the inhibitory effect of dopamine was clozapine, which is relatively D4-specific. We also found that dopamine or D1-specific agonists by themselves had no effect on cAMP production. However, dopamine inhibited the high rate of AVP-dependent cAMP production, and this effect of dopamine was reversed by clozapine but not other antagonists or by inhibitors of protein kinase C. The D4 receptor was observed in western blots of renal cortical proteins, and it was localized to the collecting duct by RT-PCR and immuno-histochemistry using a D4-specific antibody. These results show that at least a portion of the natriuretic effect of dopamine can be attributed to inhibition of AVP-dependent Na+ reabsorption by the CCD, and they introduce another signalling system as a candidate in the aetiology of low-renin, salt-dependent hypertension.
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PMID:The collecting duct, dopamine and vasopressin-dependent hypertension. 1069 7

Phospholipase D (PLD) is an enzyme involved in signal transduction and widely distributed in mammalian cells. The signal transduction pathways and role for phospholipid metabolism during hormonal response in cortical collecting duct remain partly undefined. It has been reported that dexamethasone increases transepithelial transport in M-1 cells that are derived from the mouse cortical collecting duct. We investigated the expression and activity of PLD in M-1 cells. Basal PLD activity of M-1 cells cultured in the presence of dexamethasone (5 microM) was higher than in the absence of dexamethasone. Dexamethasone and ATP activated PLD in M-1 cells but phorbol ester did not stimulate PLD activity. Vasopressin, bradykinin, dibutyryl cyclic AMP, and ionomycin were ineffective in activating PLD of the cells. The PLD2 isotype was detected by immunoprecipitation but PLD1 was not detected in M-1 cells. Addition of GTPgammaS and ADP-ribosylation factor or phosphatidylinositiol 4,5-bisphosphate to digitonin-permeabilized cells did not augment PLD activity. In intact cells PLD activity was increased by sodium oleate but there was no significant change between dexamethasone treated- and untreated cells by oleate. These results suggest that at least two types of PLD are present in M-1 cells and PLD plays a role in the corticosteroid-mediated response of cortical collecting duct cells.
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PMID:Dexamethasone enhances phospholipase D activity in M-1 cells. 1104 49

Renal cyclooxygenase 1 and 2 activity produces five primary prostanoids: prostaglandin E2, prostaglandin F2alpha, prostaglandin I2, thromboxane A2, and prostaglandin D2. These lipid mediators interact with a family of distinct G protein-coupled prostanoid receptors designated EP, FP, IP, TP, and DP, respectively, which exert important regulatory effects on renal function. The intrarenal distribution of these prostanoid receptors has been mapped, and the consequences of their activation have been partially characterized. FP, TP, and EP1 receptors preferentially couple to an increase in cell calcium. EP2, EP4, DP, and IP receptors stimulate cyclic AMP, whereas the EP3 receptor preferentially couples to Gi, inhibiting cyclic AMP generation. EP1 and EP3 mRNA expression predominates in the collecting duct and thick limb, respectively, where their stimulation reduces NaCl and water absorption, promoting natriuresis and diuresis. The FP receptor is highly expressed in the distal convoluted tubule, where it may have a distinct effect on renal salt transport. Although only low levels of EP2 receptor mRNA are detected in the kidney and its precise intrarenal localization is uncertain, mice with targeted disruption of the EP2 receptor exhibit salt-sensitive hypertension, suggesting that this receptor may also play an important role in salt excretion. In contrast, EP4 receptor mRNA is predominantly expressed in the glomerulus, where it may contribute to the regulation of glomerular hemodynamics and renin release. The IP receptor mRNA is highly expressed near the glomerulus, in the afferent arteriole, where it may also dilate renal arterioles and stimulate renin release. Conversely, TP receptors in the glomerulus may counteract the effects of these dilator prostanoids and increase glomerular resistance. At present there is little evidence for DP receptor expression in the kidney. These receptors act in a concerted fashion as physiological buffers, protecting the kidney from excessive functional changes during periods of physiological stress. Nonsteroidal anti-inflammatory drug (NSAID)-mediated cyclooxygenase inhibition results in the loss of these combined effects, which contributes to their renal effects. Selective prostanoid receptor antagonists may provide new therapeutic approaches for specific disease states.
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PMID:G protein-coupled prostanoid receptors and the kidney. 1118 68

The water channel aquaporin-2 (AQP2), a key component of the antidiuretic machinery in the kidney, is rapidly regulated by the antidiuretic hormone vasopressin. The hormone exerts its action by inducing a translocation of AQP2 from intracellular vesicles to the cell membrane. This step requires the elevation of intracellular cyclic AMP. We describe here a new method, laser scanning reflection microscopy (LSRM), suitable for determining cellular osmotic water permeability coefficient changes in primary cultured inner medullary collecting duct (IMCD) cells. The recording of vertical-reflection-mode x-z-scan section areas of unstained, living IMCD cells proved useful and valid for the investigation of osmotic water permeability changes. The time-dependent increases of reflection-mode x-z-scan section areas of swelling cells were fitted to a single-exponential equation. The analysis of the time constants of these processes indicates a twofold increase in osmotic water permeability of IMCD cells after treatment of the cells both with forskolin, a cyclic AMP-elevating agent, and with Clostridium difficile toxin B, an inhibitor of Rho proteins that leads to depolymerization of F-actin-containing stress fibers. This indicates that both agents lead to the functional insertion of AQP2 into the cell membrane. Thus, we have established a new functional assay for the study of the regulation of the water permeability at the cellular level.
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PMID:Cell volume kinetics of adherent epithelial cells measured by laser scanning reflection microscopy: determination of water permeability changes of renal principal cells. 1125 91

Fine regulation of water reabsorption by the antidiuretic hormone [8-arginine]vasopressin (AVP) occurs in principal cells of the collecting duct and is largely dependent on regulation of the aquaporin-2 (AQP2) water channel. AVP-inducible long term AQP2 expression was investigated in immortalized mouse cortical collecting duct principal cells. Combined RNase protection assay, Western blot, and immunofluorescence analyses revealed that physiological concentrations of AVP added to the basal side, but not to the apical side, of cells grown on filters induced both AQP2 mRNA and apical protein expression. The stimulatory effect of AVP on AQP2 expression followed a V(2) receptor-dependent pathway because [deamino-8-d-arginine]vasopressin (dDAVP), a specific V(2) receptor agonist, produced the same effect as AVP, whereas the V(2) antagonist SR121463B antagonized action of both AVP and dDAVP. Moreover, forskolin and cyclic 8-bromo-AMP fully reproduced the effects of AVP on AQP2 expression. Analysis of protein degradation pathways showed that inhibition of proteasomal activity prevented synthesis of AVP-inducible AQP2 mRNA and protein. Once synthesized, AQP2 protein was quickly degraded, a process that involves both the proteasomal and lysosomal pathways. This is the first study that delineates induction and degradation mechanisms of AQP2 endogenously expressed by a renal collecting duct principal cell line.
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PMID:Long term regulation of aquaporin-2 expression in vasopressin-responsive renal collecting duct principal cells. 1178 89


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