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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polyols sorbitol and inositol were determined in single freshly microdissected tubule segments of rat kidney. Twenty different structures were separated from six different kidney zones reaching from cortex to papillary tip. Picomol amounts of sorbitol and inositol were quantitated by use of an enzymatic bioluminescence procedure. Experimental conditions (700 mosmol/kg, 4 degrees C) were chosen to assure constant polyol concentrations over 3 h dissection period. Sorbitol exhibited a concentration gradient in the collecting duct system from the outer/inner medullary border (3.9 +/- 0.5 pmol/mm) to the papillary tip (78.8 +/- 6.9 pmol/mm). In the same region descending and ascending limbs of Henle's loop contained 1.5 +/- 0.5 to 5.3 +/- 1.6 pmol/mm and 2.5 +/- 0.8 to 8.35 +/- 1.5 pmol/mm, respectively. In contrast, all outer medullary and cortical structures had lower sorbitol concentrations. Inositol amounts increased continuously in the collecting duct from cortex (5.3 +/- 0.5 pmol/mm) to inner medulla (30.7 +/- 3.8 pmol/mm). This polyol was also found in thick ascending limb of Henle's loop (6.2 +/- 1.1 pmol/mm in cortex to 11.2 +/- 1.4 pmol/mm in outer medulla) and in proximal tubules (5.6 +/- 1.2 pmol/mm in S1 and 4.5 +/- 1.5 pmol/mm in S3). When related to cellular volume measured by planimetry, intracellular sorbitol concentration was calculated to be 51 mmol/l in papillary collecting duct and inositol 28 mmol/l in outer medullary thick ascending limb cells. These data confirm the role of sorbitol in the renal concentrating process in papilla. Inositol seems to have additional function in thick ascending limb of Henle's loop and the proximal tubule.
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PMID:Polyol determination along the rat nephron. 207 98

Intracellular accumulation of sorbitol, generated from D-glucose via the aldose reductase pathway, is thought to play an important role in diabetic complications such as lens cataracts and neuropathy. In order to elucidate the effect of diabetes on the renal inner medulla, another sorbitol-rich tissue, male Wistar rats were treated with a single dose of streptozotocin (60 mg/kg body weight, i.p.). Six weeks later total inner medullary tissue (IM) or isolated inner medullary collecting duct (IMCD) cells were prepared. In diabetic IM tissue, sorbitol content was 1.8-fold higher than in control IM tissue (134 +/- 17 vs. 74 +/- 22 mumol/g tissue protein). Sorbitol production in both normal and diabetic IMCD cells was strongly dependent on extracellular D-glucose concentration. In normal cells, for example, sorbitol production was 90 +/- 9 mumol sorbitol/g protein x h at 45 mM D-glucose compared to 13 +/- 1 mumol/g protein x h at 5 mM. At identical D-glucose concentrations sorbitol synthesis in diabetic IMCD cells was, however, always significantly higher than in control cells (122% of control at 15 mM and 126% of control at 45 mM). In addition, aldose reductase activity in diabetic IM was found to be augmented. The maximal velocity was 4.2 times higher (97 +/- 22 U/g protein vs. 23 +/- 7 U/g protein) while the Km of the enzyme remained unchanged. Membrane permeability for sorbitol or the response to changes in extracellular osmolarity was not significantly different in diabetic IMCD cells and normal cells with correspondingly high intracellular sorbitol concentrations. Similarly the kinetic parameters of D-glucose uptake were not altered by streptozotocin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sorbitol metabolism in inner medullary collecting duct cells of diabetic rats. 252 20

Taking into account recent results obtained with isolated papillary collecting duct cells the metabolic pathways and membrane transport systems of collecting duct cells are reviewed. The plasma membranes contain a luminal proton AT-Pase and a contraluminal Cl-/HCO3- exchanger which are involved in proton secretion; a luminal sodium channel and a contraluminal Na+/K+-AT-Pase for sodium reabsorption; a K+ channel for potassium secretion, and a Na+/K+/Cl- cotransport system for chloride transport and/or volume regulation. The plasma membranes also possess transport systems for organic substrates and organic osmolytes. D-glucose, the main substrate of the papillary collecting duct is taken up into the cell by a sodium-independent D-glucose transport system with a Km of 1.2 mM. The plasma membrane also contains mechanisms which mediate sorbitol release into the medium. This mechanism is stimulated when cells are exposed to media with a low osmolality and inhibited when cells are exposed to media with a high osmolality. D-glucose is used as metabolic substrate in anaerobic and aerobic glycolysis and as precursor for sorbitol synthesis via the aldose reductase, which is highly enriched in papillary collecting duct cells. The cells also show gluconeogenic activity as evidenced by incorporation of labeled carbon from L-alanine into glycerol, sorbitol, and myo-inositol. Accordingly, the cells show fructose-1,6-biphosphatase activity. Sorbitol synthesis in contrast to sorbitol permeability is not affected by osmolarity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Transport mechanisms and metabolic processes in isolated cells of the collecting tubule of the kidney papilla]. 284 46

Sorbitol participates in the osmoregulation of several renal cells and has also been found in isolated inner medullary collecting duct (IMCD) cells in primary culture. Therefore, osmotic regulation and distribution of sorbitol and the key enzymes of sorbitol metabolism, aldose reductase and sorbitol dehydrogenase in the renal inner medulla, were investigated in vivo under various osmotic conditions (control, diuresis, antidiuresis). In homogenates of the renal inner medulla of Wistar rats, the sorbitol content correlated with the urine osmolarity [68 +/- 12 mumol/g protein (control), 28 +/- 9 mumol/g (diuresis), 110 +/- 15 mumol/g (antidiuresis)]. Similar results were obtained for the activity of aldose reductase (sorbitol synthesis) [25 +/- 4 U/g (control), 19 +/- 3 U/g (diuresis), and 48 +/- 7 U/g (antidiuresis)]. On the contrary, the activity of sorbitol dehydrogenase (sorbitol degradation) was significantly increased to 1.26 +/- 0.42 U/g under diuretic conditions vs. control (0.84 +/- 0.14 U/g, P < 0.05). These results demonstrate the correlation between the enzymes of sorbitol synthesis and sorbitol degradation in the intact inner medulla and the urine osmolarity in vivo. Whereas the aldose reductase activity was 2.3-fold enriched in IMCD cells, the specific activity of sorbitol dehydrogenase was relatively increased in a preparation of enriched interstitial cells. This distribution was not dependent on the various diuretic conditions. These results indicate that enzymes of synthesis and of degradation of sorbitol are osmotically regulated in vivo. Therefore, the enzymatic activities of sorbitol synthesis appear to be primarily located in epithelial cells, whereas enzymatic activities of sorbitol degradation seem to be localized in interstitial cells of the renal inner medulla.
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PMID:Renal inner medullary sorbitol metabolism. 750 36

Sorbitol content was determined in porcine urinary bladder epithelial cells immediately after death of the animals and after primary culture of the cells at different osmolalities. In both instances, sorbitol content increased with urine and medium osmolality, respectively. For example, at 300 mosmol/kg the cultured cells contained 0.84 +/- 0.02 nmol/mg protein, at 600 mosmol/kg contained 21.7 +/- 0.95 nmol/mg protein, and at 900 mosmol/kg contained 59.5 +/- 2.8 nmol/mg protein. Similarly, aldose reductase activity rose from 0.27 +/- 0.04 mumol.h-1.mg protein-1 at 300 mosmol/kg to 1.81 +/- 0.16 at 600 mosmol/kg and to 3.02 +/- 0.33 at 900 mosmol/kg. These changes were, however, only observed when NaCl but not when urea was used to augment the medium osmolality, since urea equilibrated across the cell membrane. In contrast, sorbitol release from cells cultured at 900 mosmol/kg was slowest into a 900 mosmol/kg medium and fastest into a 300 mosmol/kg medium (63 +/- 16 nmol/10 min compared with 389 +/- 52 nmol/10 min). These studies demonstrate that the sorbitol content of porcine urinary bladder epithelium is regulated by changes both in sorbitol synthesis and sorbitol release. Thus the regulatory mechanisms in the urinary bladder seem to be similar to those present in the embryological related collecting duct.
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PMID:Regulation of sorbitol content in cultured porcine urinary bladder epithelial cells. 948 29

Sorbitol plays an important role in the osmoregulation of several renal cell types, especially the inner medullary collecting duct (IMCD) cells. Very little information is available concerning the expression of the enzymes of sorbitol metabolism (aldose reductase (AR) and sorbitol dehydrogenase (SDH)) on the RNA level under different osmotic conditions. We employed a RT-PCR-based strategy to investigate the regulation of mRNA coding for AR and SDH. For AR two primers (derived from the sequence of the rat eye lens) were chosen which amplify a 668-bp product. For SDH (considering the sequence of rat liver) three primers were chosen, amplifying a 367- and a 1, 068-bp fragment. Digestion with restriction enzymes and sequencing of the products clearly indicate that the specific mRNA of AR and SDH was amplified. By relative quantitative determination of the amplification products a more than 4-fold increase in mRNA for AR in IMCD cells was observed within 24 h after increasing the extracellular osmolarity from 600 to 900 mosm/l. Decreasing the osmolarity from 600 to 300 mosm/l resulted in a reduction in the mRNA level by 70%. The complete adaptation of the AR activity needed 3 (increasing osmolarity) and 6 days (decreasing osmolarity). Osmotically induced alterations in the levels of mRNA coding for SDH could not be observed. These results suggest that the adaptation of sorbitol synthesis occurs by a rapid regulation of transcription or stability of specific mRNA. For a complete synthesis or degradation of AR 3-6 days are necessary. Thus sorbitol synthesis in IMCD is more rapidly adapted to increasing osmolarities than to decreasing osmolarities.
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PMID:Rat renal expression of mRNA coding for aldose reductase and sorbitol dehydrogenase and its osmotic regulation in inner medullary collecting duct cells. 994 55

Sorbitol plays a major role in the maintenance of cell volume and functional integrity of several renal cells. Sorbitol synthesis takes place in inner collecting duct cells, whereas sorbitol dehydrogenase activity, which catalyzes the degradation of sorbitol to fructose, could mainly be detected in renal inner medullary interstitial cells. Therefore, we supposed that interstitial cells would require a sorbitol transport into the cells. However, such a transport system has not yet been described. Therefore, we have characterized the uptake of sorbitol in immortalized interstitial TK-173 cells, which were derived from human renal fibroblasts. Comparable to fresh isolated renal fibroblasts of the rat, immortalized TK-173 cells have a high sorbitol dehydrogenase activity. In this report, a temperature-dependent sorbitol uptake with saturation kinetics could be detected in immortalized TK-173 cells. The transport is characterized by a high velocity (Vmax 84 mmol/l x h) and an apparent Km of 10 mmol/l. The sorbitol uptake is independent of membrane potential, sodium, and chloride. Altogether, the physiological characteristics of this sorbitol transport are different from those of the osmotically regulated sorbitol efflux from epithelial cells. These results provide evidence that TK-173 cells derived from renal fibroblasts have a specific sorbitol transport. Furthermore, these data suggest a cooperation between epithelial and interstitial cells concerning osmoregulation.
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PMID:Evidence for a sorbitol transport system in immortalized human renal interstitial cells. 1170

Sorbitol plays an important role in the osmotic regulation of the mammalian kidney. Sorbitol synthesis is regulated by the enzyme aldose reductase (AR) and its degradation to fructose is catalyzed by the enzyme sorbitol dehydrogenase (SDH). Various data exist on the polyol pathway on the rat kidney, but little is known about the distribution of the polyol pathway enzymes in the human kidney. Determination of enzyme activities and a semiquantitative determination of mRNA expression, immunohistochemistry and in-situ hybridisation in healthy human kidney tissue was carried out. The enzyme activity of AR showed a fourfold increase from cortex to papilla, while SDH-activity dropped from cortex to papilla by a factor of four. Corresponding data was obtained at the mRNA level from the semiquantitative polymerase chain reaction (PCR). Additional differentiation at the cellular level reveals both enzymes in cells of the proximal and distal tubules, thick ascending loop, thin loop and collecting duct. Studies of enzyme activity and expression by immunohistochemistry, PCR and in-situ hybridization presented corresponding results with respect to the localization of the enzymes, which match the experimental data obtained from rats very well. Thus, the established rat model might well represent the situation in the human kidney, too.
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PMID:Localization of the polyol pathway in the human kidney. 1922 47