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 describe a patient with lithium-induced nephrogenic diabetes insipidus in whom detailed investigations of distal tubular function were performed. Clearance of free water during water diuresis was found to be augmented. This suggests proximal suppression of sodium reabsorption by lithium. Reabsorption of free water during high solute clearance was impaired. Acidification of the urine following ammonium chloride loading was abnormal, and this was corrected by sodium sulfate infusion. The cellular mechanism of lithium was investigated by means of indomethacin, an inhibitor of prostaglandin synthesis. Indomethacin caused a partial reversal of the nephrogenic diabetes insipidus, suggesting that the primary cellular action of lithium may be to inhibit the formation of cyclic AMP in the collecting duct cell, although a direct action of indomethacin in increasing solutes in the renal medulla could not be ruled out. It is possible that the lithium-induced polyuria is partially due to an enhancement by lithium of renal prostaglandin action.
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PMID:Lithium-induced nephrogenic diabetes insipidus: studies of tubular function and pathogenesis. 4 18

Mucosal acidification to pH 6.5 reduced by 88% the oxytocin- (2.2 x 10(-8) M) elicited increase of water permeability in frog urinary bladder. Mucosal alkalinization (pH 10.5) increased by as much as 200% the response to the same concentration of oxytocin. These effects were not observed when supramaximal concentrations of oxytocin were imployed. Similar changes were found when the serosal pH was modified. The hydrosmotic responses elicited by serosal hypertonicity or cyclic AMP plus theophylline were also affected by mucosal or serosal changes of the hydrogen in concentration, suggesting an effect at a post-cyclic AMP level. Important interactions were found between luminal pH and serosal hypertonicity when experimental conditions were employed similar to those observed in the collecting duct of mammalian nephron. Freeze-fracture studies showed that the number of intramembranous aggregates of particles induced by ADH in the luminal membrane was reduced by mucosal acidification and augmented by an increase in medium pH.
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PMID:Influence of mucosal and serosal pH on antidiuretic action in frog urinary bladder. 4 16

Vasopressin increases the permeability of the total urinary bladder, an analogue of the mammalian renal collecting duct, to water and small solutes, especially the amide urea. We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or the the lipophilic solute diphenylhydantoin. In contrast to their effects in vasopressin-treated bladders, the anesthetics do not inhibit cyclic AMP-stimulated water flow, consistent with an effect on vasopressin-responsive adenylate cyclase. The selectivity of the anesthetic-induced depression of water flow suggests that separate adenylate cyclases and cyclic AMP pools may exist for control of water and urea permeabilities in to toad bladder. Furthermore, theophylline's usual stimulatory effect on water flow, but not its effect on urea permeability, was entirely abolished in methoxyflurane-treated bladders, suggesting that separate phosphodiesterases that control water and urea permeabilities are present as well. We conclude that the majority of water and urea transport takes place via separate pathways across the rate-limiting luminal membrane of the bladder cell, and that separate vasopressin-responsive cellular pools of cyclic AMP appear to control permeability to water and to urea.
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PMID:Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder. 18 13

Renal tubule solute and water transport is subject to regulation by numerous factors. To characterize direct effects of the recently discovered peptide endothelin (ET) on renal tubule transport, we determined signaling mechanisms for ET effects on vasopressin (AVP)-stimulated water permeability (PF) in rat terminal inner medullary collecting duct (IMCD) perfused in vitro. ET caused a rapid, dose-dependent, and reversible fall in AVP- but not cyclic AMP-stimulated PF, suggesting that its effect on PF is by inhibition of cyclic AMP accumulation. Indomethacin did not block ET actions, ruling out a role for prostaglandins in its effect. The protein kinase C (PKC) inhibitor calphostin, or pretreatment of perfused tubules with pertussis toxin, blocked ET-mediated inhibition of AVP-stimulated PF. ET caused a transient increase in intracellular calcium ([Ca2+]i) in perfused tubules, an effect unchanged in zero calcium bath or by PT pretreatment. ET effects on PF and [Ca2+]i desensitized rapidly. Inhibition of PF was transient and largely abolished by 20 min ET preexposure, and repeat exposure to ET did not alter [Ca2+]i. In contrast, PGE2-mediated inhibition of AVP-stimulated PF and increase of [Ca2+]i were sustained and unaltered by prior exposure of IMCD to ET. Thus desensitization to ET is homologous. We conclude that ET is a potent inhibitor of AVP-stimulated water permeability in rat terminal IMCD. Signaling pathways for its effects involve both an inhibitory guanine nucleotide-binding protein and phospholipase-mediated activation of PKC. Since ET is synthesized by IMCD cells, this peptide may be an important autocrine modulator of renal epithelial transport.
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PMID:Endothelin inhibits vasopressin-stimulated water permeability in rat terminal inner medullary collecting duct. 132

Adenosine produced from 5'-AMP has been proposed as a mediator of intrinsic renal regulation. The rates of 5'-AMP and adenosine metabolism are dependent on the activities of enzyme involved in purine metabolism. The activities of adenosine kinase (AK), adenosine deaminase (ADA), 5'-nucleotidase (5'-NT), AMP deaminase, xanthine oxidase and purine nucleoside phosphorylase were measured in cytosolic and membrane fractions from glomeruli, cortical tubules, medullary thick ascending limb of Henle (MTAL) and collecting duct prepared from rat kidney by combinations of sieving and sucrose density gradient centrifugation techniques. In the cytoplasm of glomeruli cells, the activity ratios of ADA/AK and AMP deaminase/5'-NT were 70 and 2.4, respectively. The highest activity of 5'-NT was found in membrane fractions of cortical tubules where it was equally distributed between luminal and antiluminal membranes. Membrane fractions of MTAL did not contain detectable amounts of adenosine deaminase activity. The highest activity of xanthine oxidase and purine nucleoside phosphorylase was in the cytoplasm fraction of glomeruli. These results suggest that deamination of AMP and adenosine may be favored in the cytoplasm of glomeruli cells. In contrast, in the extracellular space of glomeruli and especially in the cortical tubule, AMP can be converted preferentially to adenosine by 5'-NT.
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PMID:The distribution of enzymes involved in purine metabolism in rat kidney. 161 Aug 88

We have shown that urea transport across the terminal inner medullary collecting duct (terminal IMCD) is mediated by a vasopressin-stimulated, facilitated diffusion process exhibiting properties consistent with a transporter. To investigate whether hypertonic NaCl, as exists in vivo in the inner medulla, affects urea permeability, we studied isolated perfused rat terminal IMCD segments. Perfusate and bath osmolality were varied symmetrically by adding or removing NaCl or mannitol. Urea permeability rose progressively when osmolality was increased with NaCl or mannitol from 290 to 690 mOsm/kg H2O in the absence of vasopressin; there was no further increase at 890 mOsm/kg H2O. In the presence of 10(-8) M arginine vasopressin, urea permeability increased when NaCl was added to raise osmolality from 290 to 490 mOsm/kg H2O but there was no further increase at 690 mOsm/kg H2O. When 1 mM 8-bromo cyclic AMP was added to the bath, raising NaCl still increased urea permeability. These results suggest that urea transport across the rat terminal IMCD is regulated both by vasopressin and by osmolality at values present in the renal inner medulla. Osmolality seems to activate urea transport across the rat terminal IMCD by mechanisms distinct from those of vasopressin or cyclic AMP.
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PMID:An independent effect of osmolality on urea transport in rat terminal inner medullary collecting ducts. 190 26

We used the patch-clamp technique to study the effects of ATP on the small-conductance potassium channel in the apical membrane of rat cortical collecting duct (CCD). This channel has a high open probability (0.96) in the cell-attached mode but activity frequently disappeared progressively within 1-10 min after channel excision (channel "run-down"). Two effects of ATP were observed. Using inside-out patches, low concentrations of ATP (0.05-0.1 mM) restored channel activity in the presence of cAMP-dependent protein kinase A (PKA). In contrast, high concentrations (1 mM) of adenosine triphosphate (ATP) reduced the open probability (Po) of the channel in inside-out patches from 0.96 to 0. 1.2 mM adenosine diphosphate (ADP) also blocked channel activity completely, but 2 mM adenosine 5'-[beta,gamma-imido]triphosphate (AMP-PNP), a nonhydrolyzable ATP analogue, reduced Po only from 0.96 to 0.87. The half-maximal inhibition (Ki) of ATP and ADP was 0.5 and 0.6 mM, respectively, and the Hill coefficient of both ATP and ADP was close to 3. Addition of 0.2 or 0.4 mM ADP shifted the Ki of ATP to 1.0 and 2.0 mM, respectively. ADP did not alter the Hill coefficient. Reduction of the bath pH from 7.4 to 7.2 reduced the Ki of ATP to 0.3 mM. In contrast, a decrease of the free Mg2+ concentration from 1.6 mM to 20 microM increased the Ki of ATP to 1.6 mM without changing the Hill coefficient; ADP was still able to relieve the ATP-induced inhibition of channel activity over this low range of free Mg2+ concentrations. The blocking effect of ATP on channel activity in inside-out patches could be attenuated by adding exogenous PKA catalytic subunit to the bath. The dual effects of ATP on the potassium channel can be explained by assuming that (a) ATP is a substrate for PKA that phosphorylates the potassium channel to maintain normal function. (b) High concentrations of ATP inhibit the channel activity; we propose that the ATP-induced blockade results from inhibition of PKA-induced channel phosphorylation.
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PMID:Dual effect of adenosine triphosphate on the apical small conductance K+ channel of the rat cortical collecting duct. 194 Aug 49

Differential interference contrast microscopic images were used to assess the cell volume regulatory increase (VRI) response of rat IMCD segments isolated from the mid-inner medullary region of pathogen-free Sprague-Dawley rats and perfused in vitro at 37 degrees C. In the absence of ADH. IMCD cells behaved in an osmometric fashion over the range of extracellular osmolalities 290 to 386 mOsm/kg H2O and had an osmotic space equal to 54.2% of total geometric volume. After initial shrinkage in hypertonic perfusing and bathing solutions (340 mOsm/kg H2O using sucrose), cell volume increased rapidly to the isotonic value only in tubules preincubated in ADH (100 microU/ml). The rates of VIR were: (-ADH) 0.0142 +/- 0.0046 nl.min-1.cm-1 or 0.30 +/- 0.10%/min and (+ADH) 0.7225 +/- 0.1278 nl.min-1.cm-1 or 15.42 +/- 2.31%/min (N = 4; P less than 0.01). An overshoot in cell volume was observed on return to isotonic media only in the ADH exposed tubules showing a hypertonic VRI response, indicating that IMCD cells accumulated solute during hypertonic VRI. In the absence of ADH, one mM dibutyryl cyclic AMP mimicked the effect of hormone on hypertonic VRI. This ADH-dependent VRI process required Na+ and (CO2 + HCO3-) in external media and was reduced or abolished by 0.1 mM amiloride, 0.1 mM 4,4'-diisothiocyanatostilbene-2,2-'-disulfonic acid (DIDS) in peritubular solutions. These data suggest that ADH-dependent, rapid hypertonic cell volume regulation in rat inner medullary collecting duct depends on NA+ uptake, which may be mediated by parallel Na+-H+ and an HCO3(-)-dependent. DIDS-sensitive pathway (such as, Cl+-HCO3- exchanger) in basolateral cell membrane. In addition, a luminal amiloride-sensitive pathway (most likely the cation-selective channel) may contribute to cell volume regulation in the rat IMCD.
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PMID:Rapid hypertonic cell volume regulation in the perfused inner medullary collecting duct. 255 37

To test the possibility that adenosine may be involved in a urine concentrating mechanism, effects of 1-phenylisopropyladenosine (PIA) on cyclic AMP levels have been examined in medullary thick ascending limb (mTAL) and medullary collecting duct (MCD) isolated from the rat. Low and high doses of PIA did not alter basal cyclic AMP levels in both segments. However, PIA depressed vasopressin-dependent cyclic AMP production in MCD in a dose-dependent manner: this effect of PIA was maximum at 10(-6) M. 8-Phenyltheophylline, a competitive inhibitor for adenosine receptor, completely abolished this inhibitory effect of PIA. This finding may suggest an existence of adenosine receptor on the MCD. In mTAL, PIA also suppressed vasopressin-mediated cyclic AMP generation. The present study shows an interaction between PIA and vasopressin in both MCD and mTAL. This interaction may contribute in part to urinary-concentrating disturbance in renal ischemia.
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PMID:Effect of phenylisopropyladenosine on vasopressin-dependent cyclic AMP generation in defined nephron segments from rat. 282 7

The inner medullary collecting duct (IMCD) has been proposed to be a site of atrial natriuretic factor (ANF) action. We carried out experiments in isolated perfused terminal IMCDs to determine whether ANF (rat ANF 1-28) affects either osmotic water permeability (Pf) or urea permeability. In the presence of a submaximally stimulating concentration of vasopressin (10(-11) M), ANF (100 nM) significantly reduced Pf by an average of 46%. Lower concentrations of ANF also significantly inhibited vasopressin-stimulated Pf by the following percentages: 0.01 nM ANF, 18%; 0.1 nM, 46%; 1 nM, 48%. Addition of exogenous cyclic GMP (0.1 mM) mimicked the effect of ANF, decreasing Pf by an average of 48%. ANF also inhibited cyclic AMP-stimulated Pf by an average of 31%. ANF did not affect urea permeability, nor did it alter vasopressin-stimulated cyclic AMP accumulation. We conclude that ANF at physiological concentrations causes a large inhibition of vasopressin-stimulated Pf in the rat terminal IMCD, and that cyclic GMP is the second messenger mediating the effect. ANF appears to act at a site distal to cyclic AMP generation in the chain of events linking vasopressin receptor binding to an increase in osmotic water permeability.
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PMID:Atrial natriuretic factor inhibits vasopressin-stimulated osmotic water permeability in rat inner medullary collecting duct. 284 55


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