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)

Previous evidence suggests that the activity of the mitochondrial enzyme citrate synthase [citrate oxaloacetate-lyase (pro-3S-CH(2)COO --> acetyl-CoA), EC 4.1.3.7] is increased in target tissues upon acute administration of aldosterone. Therefore, an ultramicro assay was established to determine citrate synthase levels in isolated rabbit nephron segments as a means of localizing mineralocorticoid-responsive sites within the renal cortex. The relative citrate synthase activities in normal rabbit segments (per kg of dry tissue) correlated with the metabolic activity of the segments. The order was: distal convoluted tubule > proximal convoluted tubule > cortical thick ascending limb of Henle > cortical collecting duct > pars recta. When these segments were isolated from adrenalectomized rabbits, only the citrate synthase activity in the cortical collecting duct was significantly decreased compared to normal values (3.2 mol of citrate/kg dry wt per hr compared to 7.1; P < 0.001). Furthermore, enzyme activities in segments isolated from adrenalectomized rabbits 90 min after intravenous injection of aldosterone (10 mug/kg) were unchanged from normal or adrenalectomized rabbit tubule values for all segments except the cortical collecting duct. In this segment, aldosterone significantly increased citrate synthase activity compared to adrenalectomized rabbit values (8.1 mol/kg per hr compared to 3.2; P < 0.001), in contrast to the effect of dexamethasone at 10 mug/kg (4.4 mol/kg per hr compared to 3.2; P, NS). Spirolactone SC 26304 administered 30 min prior to injection of aldosterone inhibited the increase in collecting duct citrate synthase activity seen with aldosterone alone (3.4 mol/kg per hr compared to 8.1; P < 0.001). These findings suggest that the collecting duct is the primary target for aldosterone in the renal cortex.
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PMID:Identification of mineralocorticoid target sites in the isolated rabbit cortical nephron. 693 43

4-Pentenoate (4P) is a short-chain fatty acid which causes a complete renal Fanconi syndrome. We have examined the mechanism of 4P toxicity along the nephron after a prolonged (30 min) exposition of isolated renal tubular segments to this agent. In proximal tubules, 4P inhibited the activity of alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and beta-oxidation, but not in thick ascending limb or inner medullary collecting duct tubules in suspension. These proximal effects were accompanied by a marked oxidation of the proximal redox state, with a fall in the tissue respiration and a low content of ATP. The acetyl-CoA content of proximal tubules was simultaneously reduced. Butyrate, acetate, hexanoate or octanoate did not exert these effects. In proximal tubules the metabolism of 4P led to the tissue accumulation of 3-keto-4-pentenoyl-CoA, a known unspecific inhibitor of metabolic oxidation. This metabolite was not detectable in thick ascending limbs which metabolized 4P rapidly. No metabolism of 4P was noted in collecting ducts. We conclude that beta-oxidation probably differs in proximal and thick ascending limb tubules, allowing 4P metabolism to exert a specific toxicity in proximal tubules. A selective proximal defect in energy metabolism probably explains the Fanconi syndrome observed with exposition to 4P.
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PMID:Heterogeneous metabolism and toxicity of 4-pentenoate along the dog nephron. 768 41