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)

Functionally isolated segments of rat colon and rectum were perfused in situ in a closed loop system. Rectum was defined as the lower 25--35% of the length of large intestine (cecum excluded). Perfusion conditions were optimized at 0.5 ml.min-1 and 3 cm H2O luminal pressure. Variation of perfusion rate between 0.2 and 2 ml.min-1 did not influence net volume transport (JNV). Luminal distension following elevation of hydrostatic pressure to 18 cm H2O reversibly increased Jnv. Under control conditions Jnv and Na+-transport rates (JnNa) of colon were 2--3 times higher than those of rectum. In colon transepithelial electrical potential difference (psims) was time independent --12 mV (lumen negative) whereas rectal psims increased with time from --6 mV, reaching a plateau of --67 mV within 6 h. Amiloride 10(-4) mol.l-1 had no effect on psims, Jnv, and JnNa in colon but did slightly depress K+-secretion in colon descendens. In contrast, psims in rectum was dose-dependently depressed, being reversed to +7 mV at 10(-4) mol.l-1. Jnv and JnNa were decreased by half. Acetazolamide in addition to amiloride lowered the positive post-amiloride rectal psims by half. Adrenalectomy had no effect on colonic psims, but abolished psims of the rectum. A single dose of 40 microgram.kg-1 b.w. aldosterone during the experiment restored the typical time course of rectal psims, but did not affect psims in colon. It is concluded that aldosterone induces an amiloride-sensitive Na+-pathway only in rectum, but not in colon, and that colon and rectum differ basically in their transport properties, quantitatively as well as qualitatively, as do the kidney distal convoluted tubule and the cortical collecting duct.
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PMID:Segmental heterogeneity of epithelial transport in rat large intestine. 56 27

Using the shrinking droplet method and simultaneous perfusion of the peritubular capillaries the isotonic reabsorption of Ringer's solution from the papillary collecting ducts was measured. Under control conditions the volume reabsorption from the papillary collecting ducts was Jv +/- SE = 2.6 +/- 0.1 . 10(-5) cm3 . cm-2 . s-1. In rats which were on low Na+ diet, Jv increased to 127%, and in adrenalectomized animals it decreased to 34% of the control value. Three hours after a;ocatopm pf a;dpsterpme om tje adrenalectomized animals Jv was partially restored to 63% of control rats. Amiloride 10(-4) M, added to the luminal perfusate, produced a strong inhibition of Jv (to 32% of control). Acetazolamide, 10(-4) M, added to both perfusates, reduced Jv very strongly (to 40% of control), while omission of bicarbonate reduced it only to 77% of control. Acetazolamide, added to bicarbonate-free perfusates, did not result in a significant further reduction of Jv. The data indicate that the Na+ reabsorption from the papillary collecting duct is controlled by mineralocorticoids. Furthermore, they suggest the existence of two transport mechanisms in the luminal cell membrane: 1. An amiloride-sensitive entry step and 2. an entry step via a Na+-H+-countertransport mechanism, the latter being less important.
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PMID:Sodium reabsorption in the papillary collecting duct of rats. Effect of adrenalectomy, low Na+ diet, acetazolamide, HCO-3-free solutions and of amiloride. 57 Nov 3

We measured fluoride flux (JF; pmol.min-1.mm-1) in the isolated rabbit cortical collecting duct (CCD) to investigate the determining factors of JF. The perfusate contained 100 microM fluoride and the bath was fluoride-free. Osmotically-induced lumen-to-bath water flux did not affect JF. When perfusate pH was reduced from 7.4 to 6.1 and from 6.1 to 5.0, JF increased from 0.008 +/- 0.002 to 0.027 +/- 0.007 (P less than 0.01) and from 0.018 +/- 0.003 to 0.040 +/- 0.005 (P less than 0.01), respectively. Acetazolamide at 10(-4) M in the bath reduced JF slightly though not statistically. The anion-transport inhibitor, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), at 10(-4) M in the perfusate did not affect JF. Substitution of luminal chloride with gluconate failed to affect JF in tubules from normal rabbits or from rabbits treated with deoxycorticosterone which stimulates chloride-bicarbonate exchange in the CCD. JF showed no correlation with transepithelial voltage which ranged from +4 to -104 mV. We conclude that the luminal pH represents the primary determining factor influencing JF in the rabbit CCD, and fluoride does not use a chloride-mediated or a DIDS-inhibitory transport pathway.
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PMID:Fluoride flux in the rabbit CCD: a pH-dependent event. 155 7

Short-circuit current (SCC) techniques were used to monitor the effects of various diuretic agents on Na+ transport in isolated frog skin, a model for the late distal tubule and the collecting duct of the mammalian kidney. Acetazolamide, hydrochlorothiazide, torasemide, and ethacrynic acid did not affect sodium transport (as indicated by the SCC) or transepithelial electrical resistance when added either to the apical (outer) or to the inner (basolateral, corial) bathing solution of the tissue. However, Na+ transport was sensitive to amiloride, the triamterene derivate dimethylamino-hydroxypropoxytriamterene (RPH 2823), and to furosemide. Whereas apical amiloride, and RPH 2823 induced a dose-dependent decrease in SCC and increase in transepithelial electrical resistance, apical furosemide resulted in a dose-dependent increase in SCC and a decrease in electrical resistance. None of the three diuretic agents caused a significant change in SCC when applied to the inner bathing Ringer's solution. The small furosemide-induced decrease in resistance compared with the huge increase in SCC suggests that furosemide affects Cl- permeability as well as Na+ permeability. Evidence for this notion was achieved by the following findings: The decrease in resistance after furosemide was more pronounced in tissues bathed in Cl(-)-free solutions compared with Cl(-)-containing solutions. n contrast, SCC stimulation by apical furosemide is Cl(-)-ion independent, but strongly Na+-ion dependent. SCC stimulation by furosemide is amiloride-sensitive. With respect to the onset, locus, and reversibility of action, it seems reasonable to assume that amiloride, RPH 2823, and furosemide all influence transepithelial Na+ transport by interacting with the Na+ channel or a regulator site of it within the apical membrane. The stoichiometry of the amiloride (RPH 2823)-receptor site interaction revealed Hill-coefficient(s) of less than 1, indicating a negative cooperativity among the receptor sites. The interaction between Na+ ions and amiloride or RPH 2823 displayed mixed competitive-noncompetitive inhibition. Taken together, these results support the hypothesis that amiloride and Na+ as well as RPH 2823 and Na+ may act at different loci on the apical entry mechanism in Rana esculenta skin.
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PMID:Effects of standard diuretics and RPH 2823 on transepithelial Na+ transport in isolated frog skin. 242 18

Madin Darby canine kidney (MDCK) renal epithelial cell cultures have been investigated with respect to their potency to express carbonic anhydrase activity using histochemical methods. Acetazolamide inhibitable carbonic anhydrase activity could be detected in the cytoplasmic compartment as well as in the apical membrane of cells when grown on solid culture supports. Cells forming domes in MDCK monolayers exhibit the highest histochemically detectable enzyme activity. The attempt to subculture clonal cell lines from MDCK monolayer cultures resulted in the establishment of 5 clones, slightly different with respect to size and shape of cells and their potency to form domes. Scanning electron microscopy ensured the identification of one clone (1A4), which distinctly differed from the others with respect to the apical membrane architecture. Co-localization of peanut agglutinin and carbonic anhydrase activity at the plasma membrane always revealed a combined occurrence of enzyme reactivity and lectin binding in the apical membrane domain. Both, lectin binding and carbonic anhydrase activity were distinctly more intense in plasma membrane regions equipped with microvilli. From the results it is concluded that MDCK cells in tissue culture retained properties of intercalated cells of the nephron collecting duct segment.
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PMID:Carbonic anhydrase activity in Madin Darby canine kidney cells. Evidence for intercalated cell properties. 251 53

To examine the cellular mechanisms of H+ transfer in rabbit papillary collecting duct (PCD), the 5,5-[14C]dimethyloxazolidine-2,4-dione-derived cell pH (pHi), the [3H]triphenylmethylphosphonium-derived membrane potential (Em), the lumen-to-cell Na+ concentration gradient [( Na+]o/[Na+]i), and cell potassium and chloride concentrations were studied at 37 degrees C in separated PCD from rabbits pretreated with deoxycorticosterone acetate. The variations in cell pH values were used as an index of changes in H+ secretion. Under standard conditions pHi was 7.30 +/- 0.04, [Na+]o/[Na+]i was 2.46 +/- 0.43, Em was 78 +/- 7 mV (cell negative), [K+]i was 105 +/- 10 mM, and [Cl-]i was 33 +/- 6 mM; the value of pHi thus remained higher than expected if H+ ions were passively distributed (6.13). Acetazolamide, 10(-4) M, alkalinized the cells. When [Na+]o/[Na+]i was reduced (low-Na+ medium or 10(-3) M ouabain), the cells did not acidify, suggesting that net H+ secretion did not decrease; also, pHi was not linked to the variations in the transmembrane chloride concentration gradients. When the cells were depolarized (low-Na+ medium), they became more alkaline; when the cells were hyperpolarized (10(-4) M amiloride), they became more acid; minor change in Em (ouabain) was associated with no change in pHi. It is concluded that: 1) H+ is actively secreted into the lumen; 2) active H+ secretion may not be secondary, via electroneutral Na+:H+ countertransport or HCl cotransport, but probably occurs via a primary H+ pump; 3) variations in Em probably affect pHi by acting on both the active H+ transport system and passive movements of HCO-3 (or its equivalent).
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PMID:Hydrogen transport in papillary collecting duct of rabbit kidney. 257 70

Regulation of renal erythropoietin (EPO) production is based on an intrarenal oxygen sensor. Whereas the sensitivity of this oxygen sensor to variations in renal oxygen supply is well established, the influence of changes in renal oxygen consumption has not yet been elucidated. Diuretic drugs, which inhibit active sodium reabsorption, reduce tubular oxygen consumption. We therefore investigated the effects of acetazolamide, furosemide, hydrochlorothiazide, and amiloride, known to preferentially inhibit sodium reabsorption at different segments of the nephron, on hypoxia-induced EPO formation in mice. Those drugs that are considered to act mainly in the loop of Henle, distal tubule, and collecting duct (furosemide, hydrochlorothiazide, and amiloride) did not impair EPO formation. Acetazolamide on the other hand, which is thought to act predominantly at the proximal tubular site, significantly reduced EPO formation in response to normobaric hypoxia (8 and 14% O2) and functional anemia (0.1% carbon monoxide). This inhibitory effect of acetazolamide was dose dependent and correlated with the natriuresis induced. It appeared not to depend on the metabolic acidosis induced by the drug, since the simultaneous administration of sodium bicarbonate, which restored standard bicarbonate levels to normal, did not diminish the inhibitory effect of acetazolamide on EPO production. In conclusion the data suggest that the regulation of EPO production is likely to be related to proximal tubular function.
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PMID:Regulation of erythropoietin production is related to proximal tubular function. 271 23

Acetazolamide, furosemide, chlorothiazide, and amiloride are pharmacologic agents that act primarily in the proximal tubule, loop of Henle, early distal tubule and late distal tubule and collecting duct, respectively. In order to investigate the renal pathophysiology induced by amphotericin B, these diuretic agents were used as probes of discrete segments of the nephron in the neonatal rat. Six-day-old rats were treated with amphotericin B (20 mg/kg, sc) or the vehicle. Twenty-four hours later, when evidence of amphotericin B-induced renal pathophysiology is detectable, the responses to the diuretic agents were assessed in a 2-hr clearance test, during which creatinine clearance (CCr) and the fractional excretion (FE) of water and various components of the filtrate were determined. Amphotericin B induced alterations in basal function including azotemia, hypostenuria, increases FE water and electrolytes, and a decreased FE urea (although CCr was normal). The diuretic responses to furosemide, chlorothiazide, and amiloride were not altered, indicating that the functional viability of the respective tubular segments was not affected by amphotericin B treatment. Although the maximal response to acetazolamide also remained unchanged in amphotericin B-treated pups, there was an attenuation in the half-maximal response, reflecting an apparent shift in the sensitivity to acetazolamide. All of the diuretic agents elicited an increase in urea excretion in amphotericin B-treated pups such that FE urea approached control values. Additionally, the magnitude of this increase was proportional to the magnitude of the increase in water excretion induced by each diuretic agent. These results indicate a disruption of urea recycling in the nephron and support the hypothesis that amphotericin B acts to increase the permeability of the distal tubule to urea. Thus, results from this study demonstrate the usefulness of pharmacologic agents as functional probes in the characterization of specific components of renal pathophysiology.
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PMID:Pharmacologic probing of amphotericin B-induced renal dysfunction in the neonatal rat. 336 16

Acetazolamide, furosemide, chlorothiazide and amiloride are pharmacologic agents that act primarily in the proximal tubule, loop of Henle, early distal tubule and late distal tubule and collecting duct, respectively. These diuretic agents were used to evaluate the functional integrity of discrete segments of the nephron in the neonatal rat following treatment with a known nephrotoxicant. Six-day old rats were treated s.c. with the proximal tubule toxicant mercuric chloride (1 or 3.2 mg/kg) or saline. Twenty-four hours later, when evidence of mercury nephrotoxicity is detectable, creatinine clearance and the fractional excretion of water and various components of the filtrate were determined using a 2-hr clearance period immediately after injection of a diuretic. The effects of mercury (3.2 mg/kg) were consistent with its ability to cause acute renal failure and proximal tubular necrosis and also indicated an apparent disruption of the cycling of urea in the nephron. A decrease in the fractional excretion of water, combined sodium and potassium and total osmotic solutes indicated that the diuretic response to acetazolamide was markedly attenuated in the mercuric chloride-treated pups whereas the responses to furosemide, chlorothiazide and amiloride were not altered by mercury treatment. Results from this study illustrate the specificity of these diuretics as pharmacologic probes of mercuric chloride induced renal dysfunction and, therefore, support their usefulness as tools in the investigation of renal developmental toxicity.
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PMID:Pharmacologic probing of mercuric chloride-induced renal dysfunction in the neonatal rat. 361 27

The present experiments were designed to localize the sites of carbonic anhydrase-independent bicarbonate reabsorption in the rat kidney and to examine some of its mechanisms. Young Munich-Wistar rats were studied using standard cortical and papillary free-flow micropuncture techniques. Total CO2 (tCO2) was determined using microcalorimetry. In control rats both superficial and juxtamedullary proximal nephrons reabsorbed approximately 95% of the filtered load of bicarbonate. The administration of acetazolamide (20 mg/kg body weight [bw]/h) decreased proximal reabsorption to 65.6% of the filtered load in superficial nephrons (32% was reabsorbed by the proximal convoluted tubule while 31.7% was reabsorbed by the loop segment), and to 38.4% in juxtamedullary nephrons. Absolute reabsorption of bicarbonate was also significantly higher in superficial than in juxtamedullary nephrons after administration of acetazolamide (727 +/- 82 vs. 346 +/- 126 pmol/min; P less than 0.05). The infusion of amiloride (2.5 mg/kg bw/h) to acetazolamide-treated rats increased the fractional excretion of bicarbonate as compared with animals treated with acetazolamide alone (34.9 +/- 1.9 vs. 42.9 +/- 2.1%; P less than 0.01), and induced net addition of bicarbonate between the superficial early distal tubule and the final urine (34.8 +/- 3.0 vs. 42.9 +/- 2.1%; P less than 0.05). Amiloride at this dose did not affect proximal water or bicarbonate transport; our studies localize its site of action to the terminal nephron. Vasa recta (VR) plasma and loop of Henle (LH) tubular fluid tCO2 were determined in control and acetazolamide-treated rats in order to identify possible driving forces for carbonic anhydrase-independent bicarbonate reabsorption in the rat papilla. Control animals showed a tCO2 gradient favoring secretion (LH tCO2, 7.4 +/- 1.7 mM vs. VR tCO2, 19.1 +/- 2.3 mM; P less than 0.005). Acetazolamide administration reversed this chemical concentration gradient, inducing a driving force favoring reabsorption of bicarbonate (LH tCO2, 27.0 +/- 1.4 mM vs. VR tCO2, 20.4 +/- 1.0 mM; P less than 0.005). Our study shows that in addition to the superficial proximal convoluted tubule, the loop segment and the collecting duct show acetazolamide-insensitive bicarbonate reabsorption. No internephron heterogeneity for bicarbonate transport was found in controls. The infusion of acetazolamide, however, induced significant internephron heterogeneity for bicarbonate reabsorption, with superficial nephrons reabsorbing a higher fractional and absolute load of bicarbonate than juxtamedullary nephrons. We think that the net addition of bicarbonate induced by amiloride is secondary to inhibition of voltage-dependent, carbonic anhydrase-independent bicarbonate reabsorption at the level of the collecting duct, which uncovers a greater delivery of carbonate from deeper nephrons to the collecting duct. Finally, our results suggest that carbonic anhydrase-independent bicarbonate reabsorption is partly passive, driven by favorable chemical gradients in the papillary tubular structures, and partly voltage-dependent, in the collecting duct.
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PMID:Internephron heterogeneity for carbonic anhydrase-independent bicarbonate reabsorption in the rat. 642 64

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