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)

The renal response to changes in hydration includes variation in intracellular sorbitol, a major inner medullary osmolyte. To examine the mechanism for changes in net sorbitol production, we measured activities of enzymes regulating sorbitol production (aldose reductase) and degradation (sorbitol dehydrogenase) in untreated, water diuretic, and antidiuretic (water restriction and/or vasopressin administration) rats. Collecting duct segments dissected from collagenase-treated kidneys of Sprague-Dawley rats were divided into outer medullary and three distinct inner medullary regions. Aldose reductase activity increased during antidiuresis and decreased during diuresis. In contrast, sorbitol dehydrogenase activity was very low during antidiuresis and increased during diuresis. These changes in enzyme activity were found after 3 days, but not after 1 day, of water diuresis/antidiuresis. Enzyme activity changed only in the deepest 50% of the inner medullary collecting duct. Thus, there is coordinated regulation of aldose reductase and sorbitol dehydrogenase activities so that (a) during water diuresis, aldose reductase activity decreases while sorbitol dehydrogenase activity increases; and (b) during antidiuresis (water restriction and/or vasopressin administration), aldose reductase activity increases while sorbitol dehydrogenase activity remains low. We conclude that long-term osmoregulation in response to physiologic stimuli involves both aldose reductase and sorbitol dehydrogenase activities in rat terminal inner medullary collecting duct segments.
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PMID:Coordinated response of renal medullary enzymes regulating net sorbitol production in diuresis and antidiuresis. 212 8

Streptozotocin diabetes induces a 4-fold increase in the maximal velocity of inner medullary aldose reductase as determined in vitro but increases sorbitol synthesis in intact inner medullary collecting duct (IMCD) cells only 1.3-fold. In order to resolve this discrepancy we investigated the importance of intracellular factors in controlling the role of cellular sorbitol synthesis. These factors include glucose concentration, sorbitol concentration, the activity of the NADPH-regenerating pentose phosphate pathway, intracellular NADP and NADPH content, and intracellular reduced (GSH) and oxidized glutathione (GSSG). It was found that the apparent Km of cellular sorbitol production for glucose was identical in control and diabetic rats (56 +/- 18 vs. 59 +/- 14 mmol/l D-glucose), whereas Vmax increased by 31% in diabetes. In inner medullary collecting duct cells of diabetic rats containing 146 +/- 5 mumol sorbitol/g protein, sorbitol synthesis was slightly lower (-15%), compared to cells which had been sorbitol-depleted prior to the experiment (87 +/- 4 mumol sorbitol/g protein). However, no inhibitory effect of sorbitol (up to 200 mmol/l) was observed on aldose reductase activity in vitro. In diabetic rats the content of NADPH was about 32% lower than in the control rats (3.8 +/- 0.3 vs. 5.6 +/- 0.4 mumol/g protein) and the ratio of NADPH/NADP was decreased from 25.6 +/- 5.1 to 8.6 +/- 1.7. In homogenates of the inner medulla the activity of 6-phospho-gluconate dehydrogenase (EC 1.1.1.43) was identical in both experimental groups, so the pentose phosphate shunt seems to be unaltered. GSH content in diabetic rats was also diminished (4.02 +/- 0.67 mumol/g protein vs. 7.41 +/- 0.5 mumol/g protein) and the GSH/GSSG ratio fell from 92.6 to 57.4. In enzyme tests in vitro an apparent Km of 7.3 +/- 1.9 mumol/l of the aldose reductase for NADPH was found; NADP acted as competitive inhibitor with an apparent K(i) of 183 +/- 31 mumol/l. Aldose reductase activity was also found to be strongly inhibited by the SH-group reagent p-chloromercurybenzoesulfonate (apparent K(i) = 0.85 x 10(-6) mol/l). Combining the results obtained on the properties of the aldose reductase in vitro and the observation made in the intact cells, the investigators suggest that the decrease in NADPH/NADP ratio, as well as changes in the redox state in the cells of diabetic animals, can play a significant role in the control of sorbitol synthesis.
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PMID:Control of sorbitol metabolism in renal inner medulla of diabetic rats: regulation by substrate, cosubstrate and products of the aldose reductase reaction. 824 Dec 88