Apical membrane limits urea permeation across the rat inner medullary collecting duct.

Star, Robert A.

doi:10.1172/jci114823

Cited by 42 publications

(25 citation statements)

References 31 publications

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“…Fig. 4A shows rapid osmotically induced volume changes in cortical collecting ducts from wild-type mice, with a half-time (t 1͞2 ) for osmotic equilibration of 1.09 Ϯ 0.09 s, a few times slower than the system exchange time of Ϸ0.3 s. This rapid equilibration is comparable to that measured in microperfused collecting ducts from rabbit (26) and rat (27,28) in which cell volume was deduced by tubule imaging, and perfusate exchange was accomplished in Ͻ0.1 s. Osmotic equilibration of collecting ducts from AQP3-knockout mice was significantly slower: 2.69 Ϯ 0.1 s. Because of the finite solution exchange time in our system that might underestimate the rate in tubules from wild-type mice, it is concluded that AQP3 deletion produces at least a 3-fold decrease in water permeability of the basolateral membrane of cortical collecting duct. We did not compute absolute P f values because of uncertainties in the basolateral membrane surface area exposed to the perfusate.…”

Section: Resultsmentioning

confidence: 56%

Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels

Song

Yang

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

364

251

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Aquaporin-3 (AQP3) is a water channel expressed at the basolateral plasma membrane of kidney collecting-duct epithelial cells. The mouse AQP3 cDNA was isolated and encodes a 292-amino acid water͞glycerol-transporting glycoprotein expressed in kidney, large airways, eye, urinary bladder, skin, and gastrointestinal tract. The mouse AQP3 gene was analyzed, and AQP3 null mice were generated by targeted gene disruption. The growth and phenotype of AQP3 null mice were grossly normal except for polyuria. AQP3 deletion had little effect on AQP1 or AQP4 protein expression but decreased AQP2 protein expression particularly in renal cortex. Fluid consumption in AQP3 null mice was more than 10-fold greater than that in wild-type litter mates, and urine osmolality (<275 milliosmol) was much lower than in wild-type mice (>1,200 milliosmol). After 1-desamino-8-D-arginine-vasopressin administration or water deprivation, the AQP3 null mice were able to concentrate their urine partially to Ϸ30% of that in wild-type mice. Osmotic water permeability of cortical collecting-duct basolateral membrane, measured by a spatial filtering optics method, was >3-fold reduced by AQP3 deletion. To test the hypothesis that the residual concentrating ability of AQP3 null mice was due to the inner medullary collecting-duct water channel AQP4, AQP3͞AQP4 double-knockout mice were generated. The double-knockout mice had greater impairment of urinary-concentrating ability than did the AQP3 single-knockout mice. Our findings establish a form of nephrogenic diabetes insipidus produced by impaired water permeability in collecting-duct basolateral membrane. Basolateral membrane aquaporins may thus provide blood-accessible targets for drug discovery of aquaretic inhibitors.water transport ͉ AQP3 ͉ kidney ͉ urinary-concentrating mechanism ͉ polyuria A quaporin-3 (AQP3, originally called glycerol intrinsic protein, GLIP, based on its glycerol-transport function) was cloned from rat kidney by our laboratory (1) as well as by Ishibashi et al. (2) and Echevarria et al. (3). AQP3 is a relatively weak transporter of water but functions as an efficient glycerol transporter (4). Reflection coefficient measurements (5) and mutagenesis studies (6) suggested that water and glycerol share a common pathway through the AQP3 protein, although inhibition experiments were interpreted as suggesting different pathways (7). Immunocytochemistry in rat showed AQP3 protein expression in basolateral membrane of kidney collecting duct and large airways, as well as in several tissues that are thought not to have an important water-transporting role including urinary bladder, conjunctiva, and epidermis (8-11). Recent studies report strong AQP3 expression in various regions of the gastrointestinal tract including small intestine (12). Another unique feature of AQP3 is its gene structure, which is different from the water-selective mammalian aquaporins (13). AQP3, AQP7, and AQP9 have been called ''aquaglyceroporins'' because of their relatively broad solute specificity and sequence ho...

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Section: Resultsmentioning

confidence: 56%

Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels

Song

Yang

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

364

251

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“…3) demonstrated a predominant apical localization of RUT in IMCD cells. The apical plasma membrane is rate-limiting for overall transepithelial urea transport and manifests a large increase in urea permeability in response to vasopressin (9). Our immunolocalization results therefore support the view that RUT is the "vasopressin-regulated urea transporter" of the apical plasma membrane as suggested previously from (i) the similarity between the urea transport properties of intact collecting ducts and Xenopus oocytes after injection of RUT cRNA (14) and (ii) the high level of expression of RUT mRNA in the IMCD (14).…”

Section: Discussionmentioning

confidence: 99%

“…Physiological studies in isolated perfused tubules have demonstrated that this urea transport pathway is inhibitable by phloretin and structural analogs of urea (6), and is saturable (7), providing strong evidence for the presence of a facilitated urea transporter in IMCD cells (8). Although urea transport across both apical and basolateral plasma membranes of IMCD cells appears to be mediated by phloretin-sensitive urea transporters (6,9), urea transport across the apical plasma membrane is rate-limiting for overall transepithelial urea transport and is regulated by vasopressin (9). The mechanism by which vasopressin increases urea transport across the apical plasma membrane of the IMCD has not been investigated.…”

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confidence: 99%

Cellular and subcellular localization of the vasopressin- regulated urea transporter in rat kidney.

Nielsen

Terris

Smith

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

173

162

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The renal urea transporter (RUT) is responsible for urea accumulation in the renal medulla, and consequently plays a central role in the urinary concentrating mechanism. To study its cellular and subcellular localization, we prepared affinity-purified, peptide-derived polyclonal antibodies against rat RUT based on the cloned cDNA sequence. Immunoblots using membrane fractions from rat renal inner medulla revealed a solitary 97-kDa band. Immunocytochemistry demonstrated RUT labeling of the apical and subapical regions of inner medullary collecting duct (IMCD) cells, with no labeling of outer medullary or cortical collecting ducts. Immunoelectron microscopy directly demonstrated labeling of the apical plasma membrane and of subapical intracellular vesicles of IMCD cells, but no labeling of the basolateral plasma membrane. Immunoblots demonstrated RUT labeling in both plasma membrane and intracellular vesicle-enriched membrane fractions from inner medulla, a subcellular distribution similar to that of the vasopressin-regulated water channel, aquaporin-2. In the outer medulla, RUT labeling was seen in terminal portions of short-loop descending thin limbs. Aside from IMCD and descending thin limbs, no other structures were labeled in the kidney. These results suggest that: (i) the RUT provides the apical pathway for rapid, vasopressinregulated urea transport in the IMCD, (ii) collecting duct urea transport may be increased by vasopressin by stimulation of trafficking of RUT-containing vesicles to the apical plasma membrane, and (iii) the rat urea transporter may provide a pathway for urea entry into the descending limbs of short-loop nephrons.Rapid, passive urea absorption from the inner medullary collecting duct (IMCD) is responsible for generation of high urea concentrations in the inner medullary interstitium (1) and consequently plays a central role in the urinary concentrating mechanism (2). The rate of absorption is accelerated by vasopressin (3, 4) via increases in intracellular cyclic AMP (5). Physiological studies in isolated perfused tubules have demonstrated that this urea transport pathway is inhibitable by phloretin and structural analogs of urea (6), and is saturable (7), providing strong evidence for the presence of a facilitated urea transporter in IMCD cells (8). Although urea transport across both apical and basolateral plasma membranes of IMCD cells appears to be mediated by phloretin-sensitive urea transporters (6, 9), urea transport across the apical plasma membrane is rate-limiting for overall transepithelial urea transport and is regulated by vasopressin (9). The mechanism by which vasopressin increases urea transport across the apical plasma membrane of the IMCD has not been investigated. In general, there are two possible mechanisms. (i) As has been demonstrated for the vasopressin-regulated water channel (10-13), the urea permeability of the apical plasma membrane may be increased as a result ofvasopressin-stimulated insertion of urea-transporter-containing vesicles into the apical p...

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“…Therefore, the accumulation of UT in the apical plasma membrane of the collecting tubule is important and most likely functions as a rate-limiting step for urea reabsorption in the houndshark kidney. In the mammalian kidney, the apical plasma membrane of IMCD was found to be the rate-limiting membrane for overall transepithelial transport of water and urea (105). Accumulation of the UT-A1 to the apical plasma membrane is a key step for the regulation of urea transport in the IMCD (64).…”

Section: Urea Retention In the Kidney: Urea Transportermentioning

confidence: 99%

Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption

Hyodo

Kakumura

Takagi

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption. Am J Physiol Regul Integr Comp Physiol 307: R1381-R1395, 2014. First published October 22, 2014 doi:10.1152/ajpregu.00033.2014.-For adaptation to highsalinity marine environments, cartilaginous fishes (sharks, skates, rays, and chimaeras) adopt a unique urea-based osmoregulation strategy. Their kidneys reabsorb nearly all filtered urea from the primary urine, and this is an essential component of urea retention in their body fluid. Anatomical investigations have revealed the extraordinarily elaborate nephron system in the kidney of cartilaginous fishes, e.g., the four-loop configuration of each nephron, the occurrence of distinct sinus and bundle zones, and the sac-like peritubular sheath in the bundle zone, in which the nephron segments are arranged in a countercurrent fashion. These anatomical and morphological characteristics have been considered to be important for urea reabsorption; however, a mechanism for urea reabsorption is still largely unknown. This review focuses on recent progress in the identification and mapping of various pumps, channels, and transporters on the nephron segments in the kidney of cartilaginous fishes. The molecules include urea transporters, Na, and aquaporins, which most probably all contribute to the urea reabsorption process. Although research is still in progress, a possible model for urea reabsorption in the kidney of cartilaginous fishes is discussed based on the anatomical features of nephron segments and vascular systems and on the results of molecular mapping. The molecular anatomical approach thus provides a powerful tool for understanding the physiological processes that take place in the highly elaborate kidney of cartilaginous fishes. cartilaginous fish; kidney; osmoregulation; transporters; urea BODY FLUID REGULATION is essential for all organisms to survive in their respective habitats, including freshwater (FW), seawater (SW), and terrestrial environments. It is well known that teleost fish regulate their plasma Na ϩ and Cl Ϫ concentrations and osmolality at levels about one-third of SW. Meanwhile, cartilaginous fishes (sharks, skates, rays, and chimaeras) have adopted a unique osmoregulatory strategy for adaptation to the high-salinity marine environment. Cartilaginous fishes control plasma ions to levels approximately one-half of surrounding SW while they store high concentrations of the nitrogenous compound urea as an osmolyte (the so-called "ureosmotic strategy"). As a result, their body fluids are slightly hyperosmotic to surrounding SW (for instance, plasma osmolality of houndshark is 1,000 mosmol/kg H 2 O in SW of 988 mosmol/kg H 2 O; Ref. 53), and thus cartilaginous fishes do not typically suffer dehydration even in the high-osmolality SW environment. To maintain high concentration of urea in the body, urea production by the ornithine urea cycle (OUC) is essential. Investigations on the OUC enzymes have proved that the liver is the primary organ f...

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Apical membrane limits urea permeation across the rat inner medullary collecting duct.

Cited by 42 publications

References 31 publications

Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels

Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels

Cellular and subcellular localization of the vasopressin- regulated urea transporter in rat kidney.

Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption

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