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

The stop-flow technique was used in dogs to determine the site of entry of urinary prostaglandins (PG) into tubular fluid. The proximal tubule was localized by the peak (U/PPAH)/(U/PIn) and the distal tubule and collecting duct by the peak U/PIn and the minimum (U/PNa)/(U/PIn). The peak of prostaglandin E (PGE) concentration was located 4.8+/-0.8 (SEM) ml distal to the proximal tubule and 4.6+/-0.8 (SEM) ml proximal to the distal nephron. At its peak, PGE was concentrated 6.3-fold over baseline, whereas inulin was concentrated 1.4-fold at its peak. The height of the PGE peak but not its location was increased by an i.v. infusion of angiotensin II at 20 ng/kg of body wt per min. Indomethacin abolished the PG peak. In a single experiment, prostaglandin F2alpha (PGF2alpha) exhibited an excretion pattern similar to PGE. These data indicate that the site of entry of PG into tubular fluid is most likely in the loop of Henle. This is consistent with the hypothesis that PG synthesized in the medulla can be transported to the cortex via tubular fluid. Whether PG in the tubular fluid can influence renal function remains to be determined.
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PMID:Urinary prostaglandins: site of entry into renal tubular fluid. 85 73

Blood-perfused isolated dog kidneys demonstrate steady increases in blood flow and in water and sodium excretion which could be attributed to the accumulation of renal prostaglandins in the perfusing blood. This hypothesis was tested by adding indomethacin, a potent inhibitor of prostaglandins synthesis, to the perfusing blood. Indomethacin completely prevented the vasodilation observed in control kidneys, without affecting glomerular filtration rate. Urine volume was not modified but sodium excretion was enhanced while the steady free water clearance increment observed in the control kidneys was depressed by indomethacin. The sum of sodium and free water clearances which, in the absence of antidiuretic hormone, constitutes an index of the part of the filtered load of solutes which escapes proximal tubular reabsorption, was not modified by indomethacin. Finally, indomethacin partially maintained the osmotic cortico-papillary gradient which was abolished after 2 hrs perfusion in control kidneys. These data suggest that prostaglandins accumulation in the blood is probably the major cause of the vasodilation taking place in isolated blood-perfused kidneys. This vasodilation does not account for decreased proximal reabsorption but partially explains the ADH-resistant diabetes insipidus developing in the isolated kidney. Moreover, indomethacin inhibits sodium reabsorption in the ascending limb of Henle's loop and increases water transport in the collecting duct.
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PMID:Effects of indomethacin on renal hemodynamics and on water and sodium excretion by the isolated dog kidney. 123 89

1. To further explore the Na(+)-retaining effect of indomethacin along the whole length of the nephron, the Na(+)-K(+)-ATPase activity of isolated tubules from indomethacin-pretreated rats was compared with that of tubules isolated from intact rats and exposed directly to prostaglandin E2. 2. Indomethacin increased Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (+24%, P < 0.001 versus control), proximal straight tubule (+75%, P < 0.001 versus control), medullary thick ascending limb (+68%, P < 0.001 versus control), cortical thick ascending limb (+7%, not significant) and cortical collecting duct (+18%, P < 0.025 versus control). In contrast, in the distal convoluted tubule indomethacin decreased Na(+)-K(+)-ATPase activity by -42% (P < 0.001 versus control). 3. Indomethacin also strongly increased Na(+)-K(+)-ATPase activity in the cortical collecting duct of adrenalectomized rats. 4. In isolated tubules from control rats, prostaglandin E2 reduced Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (-33%, P < 0.05), proximal straight tubule (-60%, P < 0.001), medullary thick ascending limb (-43%, P < 0.001), cortical thick ascending limb (-25%, P < 0.001) and cortical collecting duct (-45%, P < 0.001) and in the distal convoluted tubule, prostaglandin E2 increased Na(+)-K(+)-ATPase activity (+32%, P < 0.05). 5. That these changes in Na(+)-K(+)-ATPase activity in indomethacin-pretreated rats and prostaglandin E2-treated controls are similar in magnitude but occur in opposite directions suggests that the response to indomethacin is mediated by inhibition of prostaglandin E2 synthesis in the nephron. In the cortical collecting duct the effect of indomethacin is aldosterone-independent.
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PMID:Indomethacin and sodium retention in the rat: role of inhibition of prostaglandin E2 synthesis. 132 47

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

The effect of prostaglandin on diffusional water permeability has been studied in collecting ducts in an isolated rat papilla. PGE2 increased water permeability. The effect was significant at a concentration of 10(-8) mol 1(-1) and was maximal with a concentration of 10(-6) mol 1(-1). The maximal increment of 0.94 +/- 0.10 (SEM) micron s-1 was approximately half that produced by maximal stimulation with antidiuretic hormone (2.18 +/- 0.12 micron s-1). A concentration of 10(-8) mol 1(-1) produced an increase in basal water permeability and 24 mu unit ml-1 ADH, which without PGE2 present gave a similar increase, had no incremental effect. ADH 100 mu unit ml-1 increased permeability to a value similar to that observed in the absence of PGE2. Thus PGE2 and ADH both increase water permeability but the increments are not additive. Indomethacin in a concentration that inhibited prostaglandin production altered the response of the collecting duct to ADH. The dose response curve was shifted to the left and the maximal increase in water permeability and the lowest dose at which a response occurred took place at concentrations less than 1/2 those required in its absence. Prostaglandins influence the action of ADH and it is likely that in life they regulate and modulate the change in water permeability induced by anti-diuretic hormone.
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PMID:The effect of prostaglandin E2 and ADH on diffusional water permeability in collecting duct of an isolated rat papilla. 694 74

These studies were conducted to determine if the prostaglandin-synthesis inhibitor indomethacin or the protein kinase C (PKC) inhibitor staurosporine affect the inhibition of osmotic water permeability (Pf) by the alpha-2 (alpha 2) agonist dexmedetomidine in the rat inner medullary collecting duct (IMCD). Terminal IMCDs from Wistar rats were perfused and Pf was increased with either 220 pM arginine vasopressin (AVP) or 0.1 mM 8-chlorophenylthio cyclic adenosine monophosphate (8CPTcAMP). All agents were added to the bathing solution. Dexmedetomidine at 100 nM inhibited both AVP- and 8CPTcAMP-stimulated Pf. When Pf was increased by AVP, indomethacin at 0.1 mM or 5 microM reversed the dexmedetomidine-induced inhibition by 68% and 43%, respectively. When Pf was increased by 8CPTcAMP, indomethacin at 0.1 mM or 5 microM reversed inhibition by 83% and 70%, respectively. Indomethacin increased AVP and 8CPTcAMP-stimulated Pf by 20 to 30% and dexmedetomidine inhibited the AVP+ indomethacin-stimulated Pf. Staurosporine at 10 nM yielded similar results. Results suggest that PKC and prostaglandins are involved in the alpha 2 mediated mechanism, and staurosporine and indomethacin-sensitive cellular mediators modulate basal Pf.
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PMID:Indomethacin and staurosporine reverse alpha 2 inhibition of water transport in rat IMCD. 935 Jun 58

PGE(2) inhibits osmotic water permeability (P(f)) in the rat inner medullary collecting duct (IMCD) via cellular events occurring after the stimulation of cAMP, i.e., post-cAMP-dependent events. The alpha(2)-agonists also inhibit P(f) in the rat IMCD via post-cAMP-dependent events. The purpose of this study was to determine whether PGE(2) plays a role in alpha(2)-mediated inhibition of P(f), Na(+), and urea transport in the rat IMCD. Isolated terminal IMCDs from Wistar rats were perfused to measure, in separate experiments, P(f), lumen-to-bath (22)Na(+) transport (J(lb)), and urea permeability (P(u)). Transport was stimulated with 220 pM arginine vasopressin (AVP) or 0.1 mM 8-(4-chlorophenylthio)-cAMP (CPT-cAMP). Indomethacin was used to inhibit endogenous prostaglandin synthesis, and the alpha(2)-agonists clonidine, oxymetazoline, and dexmedetomidine were used to test the role of PGE(2) in the alpha(2)-mediated mechanism that inhibits transport. All agents were added to the bath. Indomethacin at 5 microM significantly elevated CPT-cAMP-stimulated P(f), J(lb), and P(u), and subsequent addition of 100 nM PGE(2) reduced these transport parameters. Indomethacin reversed alpha(2) inhibition of CPT-cAMP-stimulated P(f), J(lb), and P(u), and subsequent addition of PGE(2) reduced transport in each case. Indomethacin partially reversed alpha(2) inhibition of AVP-stimulated P(f), J(lb), and P(u), and PGE(2) reduced transport back to the alpha(2)-inhibited level. These results indicate that PGE(2) is a second messenger involved in the mechanism of transport inhibition mediated by alpha(2)-adrenoceptors via post-cAMP-dependent events in the rat IMCD.
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PMID:Role of PGE(2) in alpha(2)-induced inhibition of AVP- and cAMP-stimulated H(2)O, Na(+), and urea transport in rat IMCD. 1091 49