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)

The effects of acidosis and mineralocorticoids on cellular H+/HCO3- transport mechanisms were examined in intercalated cells of the outer stripe of outer medullary collecting duct (OMCDo) from rabbit. Intracellular pH (pHi) of intercalated cells was monitored by fluorescence ratio imaging using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). pHi recovered from an acid load at 2.8 +/- 0.5 x 10(-3) pHU/s in the absence of ambient Na+. This pHi recovery rate was similar in chronic acidosis induced by NH4Cl loading, but it was enhanced (+111%) by treatment with deoxycorticosterone acetate (DOCA). In a DOCA-treated group, luminal 10 microM SCH28080 and 0.1 mM omeprazole, H(+)-K(+)-ATPase inhibitors, did not change the pHi recovery rate, while luminal 0.5 mM N-ethylmaleimide blocked the rate by 68%. DOCA, but not acidosis, increased (approximately 40%) initial pHi response to bath HCO3- or Cl- reduction in Na(+)-free condition. After an acid load in the absence of Na+ and HCO3-, pHi response to basolateral Na+ addition was stimulated (+66%) by acidosis, but not by DOCA. Our results suggest that (a) mineralocorticoids stimulate H+/HCO3- transport mechanisms involved in transepithelial H+ secretion, i.e., a luminal NEM-sensitive H+ pump and basolateral Na(+)-independent Cl(-)-HCO3- exchange; and (b) acidosis enhances the activity of basolateral Na(+)-H+ exchange that may be responsible for pHi regulation.
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PMID:Mineralocorticoids and acidosis regulate H+/HCO3- transport of intercalated cells. 131 49

Endothelins may be important regulators of renal inner medullary collecting duct (IMCD) function. These peptides are secreted in large amounts by IMCD cells and can, in turn, potently inhibit sodium and water transport systems in the IMCD. This study characterized endothelin (ET) receptors in the IMCD in order to gain insight into this unique renal autocrine system. Radioligand binding studies with 125I-ET-1 yielded a B(max) of 205.7 fmol/mg and a KD of 218 pM for ET-1. Similar studies with 125I-ET-3 yielded two populations of receptors for ET-3, one with a KD of 50 pM and one with a KD of 920 pM. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of IMCD cells covalently labeling with 125I-ET-1 yielded two bands, one at 97 kDa with affinities of ET-1 greater than ET-2 much greater than ET-3 and one at 47 kDa with affinities ET-1 greater than or equal to ET-2 = ET-3. Reverse transcription and polymerase chain reaction revealed the presence of both endothelin receptor types A and B. These data indicate that IMCD cells have high affinity, high density receptors for endothelin and express both known types of endothelin receptor.
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PMID:Characterization of endothelin receptors in the inner medullary collecting duct of the rat. 131 15

Previous data suggest that atrial natriuretic factor (ANF) and bradykinin (BK) interact to increase Na+ and water excretion. We propose that this interaction is due to a synergistic action that inhibits Na+ absorption in the distal nephron. We examined the effects of BK and ANF on transport by monolayers of a cortical collecting duct cell line, M-1. BK (10(-8) M) had no effect on short-circuit current (Isc). Similarly, ANF (10(-8) M) did not inhibit Isc. In contrast, Isc decreased by 18% (from 57 +/- 8 to 46 +/- 6 microA/cm2) when BK and ANF were added simultaneously at this concentration (P less than 0.05). Because guanosine 3',5'-cyclic monophosphate (cGMP) and protein kinase C are implicated in the second messenger cascades of ANF and BK, we investigated their potential roles in mediating this interaction. Dibutyryl-cGMP (10(-4) M) inhibited Isc from 33 +/- 4 to 22 +/- 3 microA/cm2 (P less than 0.05) in the presence of BK but not in its absence. Staurosporine and calphostin C, inhibitors of protein kinase C, completely blocked the decrease in Isc caused by simultaneous addition of ANF and BK. cAMP levels in M-1 cells were not affected by either ANF alone or BK alone; however, when cultures were treated with both hormones, cAMP decreased from 856 +/- 56 to 332 +/- 26 fmol/10(6) cells (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ANF and bradykinin synergistically inhibit transport in M-1 cortical collecting duct cell line. 132 53

Experimental nephrotic syndrome results in sodium retention, reflecting, at least in part, an intrinsic defect in renal sodium handling in the distal nephron. We studied the relationships among plasma atrial natriuretic peptide (ANP) concentration, sodium excretion (UNaV), and urinary cyclic GMP excretion (UcGMPV) in vivo, and the responsiveness of isolated glomeruli and inner medullary collecting duct (IMCD) cells to ANP in vitro, in rats with adriamycin nephrosis (6-7 mg/kg body weight, intravenously). 3-5 wk after injection, rats were proteinuric and had a blunted natriuretic response to intravenous infusion of isotonic saline, 2% body weight given over 5 min. 30 min after onset of the infusion, plasma ANP concentrations were elevated in normals and were even higher in nephrotics. Despite this, nephrotic animals had a reduced rate of UcGMPV after the saline infusion, and accumulation of cGMP by isolated glomeruli and IMCD cells from nephrotic rats after incubation with ANP was significantly reduced compared to normals. This difference was not related to differences in binding of 125I-ANP to IMCD cells, but was abolished when cGMP accumulation was measured in the presence of 10(-3) M isobutylmethylxanthine or zaprinast (M&B 22,948), two different inhibitors of cyclic nucleotide phosphodiesterases (PDEs). Infusion of zaprinast (10 micrograms/min) into one renal artery of nephrotic rats normalized both the natriuretic response to volume expansion and the increase in UcGMPV from the infused, but not the contralateral, kidney. These results show that, in adriamycin nephrosis, blunted volume expansion natriuresis is associated with renal resistance to ANP, demonstrated both in vivo and in target tissues in vitro. The resistance does not appear related to a defect in binding of the peptide, but is blocked by PDE inhibitors, suggesting that enhanced cGMP-PDE activity may account for resistance to the natriuretic actions of ANP observed in vivo. This defect may represent the intrinsic sodium transport abnormality linked to sodium retention in nephrotic syndrome.
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PMID:Cellular basis for blunted volume expansion natriuresis in experimental nephrotic syndrome. 132 96

It has recently been discovered that both mineralocorticoid (MC) and glucocorticoid (GC) hormones can stimulate electrogenic Na+ absorption by mammalian collecting duct cells in culture. In primary cultures of rat inner medullary collecting duct (IMCD) cells, 24-h incubation with either MC or GC agonist stimulates Na+ transport approximately threefold. We have now determined that the effects were not additive, but the time courses were different. As aldosterone is known to stimulate citrate synthase, Na+/K+ ATPase activity, and ouabain binding in cortical collecting duct principal cells, we determined the effects of steroids on these parameters in IMCD cells. MC and GC agonists both produced a small increase in citrate synthase activity. There was no increase in Na+/K+ ATPase activity but specific ouabain binding was increased more than two-fold by either agonist. To determine the role of apical Na+ entry in the steroid-induced effects, the Na+ channel inhibitor, benzamil, was used. Benzamil did not alter the stimulation of citrate synthase activity by either steroid. In contrast, GC stimulation of ouabain binding was prevented by benzamil, whereas MC stimulation was not. We conclude that there are differences in the way that MC and GC hormones produce an increased Na+ transport. Both appear to produce translocation (or activation) of pumps into the basolateral membrane. GC stimulation of pump translocation requires increased Na+ entry whereas MC stimulation does not.
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PMID:Cellular responses to steroids in the enhancement of Na+ transport by rat collecting duct cells in culture. Differences between glucocorticoid and mineralocorticoid hormones. 132 98

Microelectrode techniques were used to determine the Na+ and K+ transport properties of the collecting duct cell in the isolated cortical collecting duct (CCD) from rabbits 14 d after uninephrectomy (UNX); results were compared with those from sham-operated rabbits (control). UNX had no effects on plasma aldosterone levels. The CCDs from UNX rabbits exhibited structural hypertrophy. The lumen negative transepithelial voltage and the basolateral membrane voltage (VB) were elevated in the UNX group. Although the transepithelial conductance (GT) and the fractional apical membrane resistance (fRA) were not different between the two groups, the conductances of the apical and the basolateral membranes were increased, and the tight junction conductance was decreased in the UNX group. The amiloride-sensitive changes in apical membrane voltage (VA), fRA, and GT were greater in the UNX group. The changes in VA upon raising the perfusate K+ concentration and the changes in VA and GT upon addition of Ba2+ to the perfusate were elevated in the UNX group. Upon raising K+ in the bath, a large depolarization of VB was observed in the UNX group. Lowering the bath Cl- resulted in a small depolarization of VB in the UNX group. Addition of Ba2+ to the bath in the UNX group caused the VB to hyperpolarize in parallel with decreases in GT and fRA whereas in the control group it had no effect on VB. Addition of ouabain to the bath resulted in a large depolarization of VB in the UNX group. We conclude that (a) UNX stimulates conductances of Na+ and K+ in the apical membrane, active Na(+)-K+ pump activity, and K+ conductance in the basolateral membrane, independently of plasma aldosterone; (b) The basolateral membrane in the tubules of UNX rabbits is more selective to K+; and (c) the hyperpolarization of VB upon UNX may increase passive K+ entry into the cell across the basolateral membrane.
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PMID:Effects of uninephrectomy on electrical properties of the cortical collecting duct from rabbit remnant kidneys. 132 1

The effects of prostaglandin (PG) E2 on cell swelling were studied in isolated perfused tubules of rabbit kidney. PGE2 (1 microM) added to the bath induced cell swelling by 13.4, 7.2, and 9.6% in the connecting tubule, distal convoluted tubule, and cortical collecting duct, respectively, but it had no effect on the proximal convoluted tubule and cortical thick ascending limb. The response was dose dependent in the range of 1 nM to 1 microM. PGI2 exerted a similar effect, but PGF2 alpha had no effect. The swelling was completely blocked by basolateral Na+ removal and was attenuated by bilateral Cl- removal, suggesting that the swelling was mediated by basolateral Na+ entry in association with Cl- entry. In all segments except proximal tubule, PGE2 caused an initial transient peak followed by a sustained increase in intracellular Ca2+. Intracellular Ca2+ chelation or inhibition of Ca2+ release from intracellular stores abolished the PGE2-induced cell swelling, but extracellular Ca2+ removal did not. An inhibitor of the Na(+)-Ca2+ exchanger (3',4'-dichlorobenzamil, 100 microM) in the bath completely inhibited PGE2-induced cell swelling. Neither furosemide (1 mM) nor amiloride (1 mM) added to bath abolished the response, indicating that neither Na(+)-K(+)-2Cl- cotransport nor Na(+)-H+ exchange is involved in the action of PGE2. The swelling response to PGE2 was observed even in the presence of ouabain, indicating that the effect of PGE2 is independent of Na(+)-K(+)-adenosinetriphosphatase inhibition. Nicardipine added to bath partially inhibited the swelling response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of PGE2-induced cell swelling in distal nephron segments. 133 3

Whole cell patch-clamp techniques were used to characterize the electrophysiological properties of cells from the inner stripe portion of the rabbit outer medullary collecting duct (OMCDi) grown in primary culture. With pipette and bathing solutions mimicking intracellular and extracellular fluid, the resting membrane voltage was -30 to -40 mV. The whole cell conductance exhibited slight outward rectification, and at the resting membrane voltage the cell conductance averaged 2.58 +/- 0.49 nS (n = 17). The major conductive ion species was Cl-. The Cl- conductance was also found to have a significant permeability to HCO3- and was inhibited by the Cl(-)-channel blockers diphenylamine carboxylic acid and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. A small K+ conductance was also present, but no Na+ conductance was detected. Current generated by the H(+)-adenosinetriphosphatase (H(+)-ATPase) was quantitated. This current was dependent on the presence of ATP in the pipette. Dicyclohexylcarbodiimide, N-ethylmaleimide, and bafilomycin A1, inhibitors of the vacuolar H(+)-ATPase, also reduced this outward current in an ATP-dependent manner. The inhibitor-sensitive component of the outward current, a measure of the current generated by the H(+)-ATPase, was in the range of 35-100 pA/cell.
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PMID:Electrophysiological properties of cultured outer medullary collecting duct cells. 133 7

Dopamine decreases tubular sodium reabsorption, attributed in part to Na/K-ATPase inhibition in the proximal convoluted tubule (PCT). Because the final regulation of sodium excretion occurs in the collecting duct, where we have demonstrated specific dopamine DA1 binding sites, we examined the effects of dopamine, and of DA1 and DA2 receptor agonists on the Na/K pump in the microdissected rat cortical collecting duct (CCD) and in Madin-Darby canine kidney (MDCK) cells, a line derived from the dog distal nephron. Dopamine inhibited pump activity in CCD by approximately 40%-50%, an effect proportionally larger than in the PCT. Unlike in the latter, the effect of dopamine was reproduced by the DA1 agonist fenoldopam, which inhibited the CCD pump in dose-dependent manner (maximum, 10 microM). The DA2 agonist quinpirole was without effect, either alone or in combination with fenoldopam. These actions on Na/K-ATPase paralleled in reciprocal fashion effects on adenylate cyclase: dopamine or fenoldopam, but not quinpirole, produced a significant increase in cAMP content, and the stimulation by dopamine was blocked by SCH 23390. Inhibitors of cAMP phosphodiesterase (3-isobutyl-1-methyl-xanthine and theophylline), as well as forskolin and dibutyryl-cAMP, mimicked the effect of dopamine on the pump, underscoring the role of increased cAMP in this phenomenon. Both dopamine and fenoldopam inhibited Na/K-ATPase activity in MDCK cells. The results indicate that besides the PCT dopamine inhibits Na/K-ATPase activity in cells of the distal nephron, where its effect on the pump appears to be more pronounced and is mediated by activation of the DA1 receptor. The natriuretic effect of dopamine is probably exerted at both proximal and distal nephron sites.
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PMID:Dopamine inhibits Na/K-ATPase in single tubules and cultured cells from distal nephron. 135 25

Mechanisms of Na+ entry across the luminal membrane of the rabbit connecting tubule (CNT) and cortical collecting duct (CCD) were investigated in vitro by analyzing factors that block the ouabain-induced tubular swelling. In the CNT and CCD, cell swelling caused by 100 microM ouabain added to the bath was completely blocked by luminal Na+ removal, suggesting that the main factor inducing cell swelling is Na+ entry through the luminal membrane. Trichlormethiazide (100 microM) and amiloride (10 microM) inhibited the swelling in CNT when applied in combination to the lumen, but not when given separately. The swelling was also inhibited by Cl- omission from the lumen in the presence of amiloride. By contrast, no effect was noted when furosemide (100 microM), 4-acetamide-4'-isothiocyanatostilben-2,2'-disulfonic acid (1 mM) or 5-(N-ethyl-N-isopropyl)amiloride (100 microM) was added to the lumen in the presence of amiloride, indicating the absence of any influence of the Na(+)-K(+)-2Cl- cotransporter and the parallel Na+/H+, Cl-/HCO3- exchanger. The cell swelling in the CCD was blocked by luminal addition of amiloride alone with no effect from trichlormethiazide. In CNT, when the ouabain-induced cell swelling was prevented by both diuretics, addition of parathyroid hormone (PTH, 3 nM) to the bath induced cell swelling, suggesting that another Na+ entry pathway is newly generated by PTH. These results demonstrate that ouabain-induced cell swelling depends on Na+ entry across the luminal membrane. In the CNT, the pathways include an amiloride-sensitive Na+ channel, thiazide-sensitive Na(+)-Cl- cotransport and a PTH-stimulated Na+ pathway, whereas the CCD has only the amiloride-sensitive Na+ channel.
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PMID:Ouabain-induced cell swelling in rabbit connecting tubule: evidence for thiazide-sensitive Na(+)-Cl- cotransport. 140 55

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