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 studies have indicated that NO synthesis in isolated inner medullary collecting duct cells is reduced by cationic amino acids that compete with L-arginine for cellular uptake. In the present study, we investigated the effects of chronic renal medullary infusion of cationic amino acids on renal NO concentration and mean arterial pressure (MAP) in Sprague-Dawley rats. Renal medullary infusion of L-ornithine (50 microg/kg per min) or L-lysine (50 microg/kg per min) markedly decreased NO in the medulla (vehicle, 124 +/- 11 nmol/L; L-ornithine, 45 +/- 4 nmol/L; L-lysine, 42 +/- 6 nmol/L) and increased MAP (vehicle, 111 +/- 7 mm Hg; L-ornithine, 143 +/- 6 mm Hg; L-lysine, 148 +/- 3 mm Hg) after 5 days of infusion. In contrast, intravenous infusion of the same dose of L-ornithine or L-lysine for 5 days increased plasma concentration to levels similar to those observed with intramedullary infusion but did not change NO in the medulla or alter MAP. Furthermore, the NO-suppressing and hypertensive effects of medullary interstitial infusion of L-ornithine (50 microg/kg per min) were attenuated by simultaneous infusion of L-arginine (500 microg/kg per min; NO, 97 +/- 10 nmol/L; MAP, 124 +/- 3 mm Hg). A 5-day infusion of an antisense oligonucleotide against CAT-1 (18-mer, 8.3 nmol/h) significantly decreased CAT-1 protein in the medulla, decreased NO in the medulla (scrambled oligo, 124 +/- 10 nmol/L; antisense oligo, 67 +/- 11 nmol/L), and increased MAP (scrambled oligo, 113 +/- 2 mm Hg; antisense oligo, 130 +/- 2 mm Hg). These results suggest that uptake of L-arginine by cationic amino acid transport systems in the renal medulla plays an important role in the regulation of medullary NO and MAP in rats.
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PMID:Cationic amino acid transport in the renal medulla and blood pressure regulation. 1184 99

Epithelial sodium channels (ENaCs) mediate Na(+) entry across the apical membrane of high resistance epithelia that line the distal nephron, airway and alveoli, and distal colon. These channels are composed of three homologous subunits, termed alpha, beta, and gamma, which have intracellular amino and carboxyl termini and two membrane-spanning domains connected by large extracellular loops. Maturation of ENaC subunits involves furin-dependent cleavage of the extracellular loops at two sites within the alpha subunit and at a single site within the gamma subunit. The alpha subunits must be cleaved twice, immediately following Arg-205 and Arg-231, in order for channels to be fully active. Channels lacking alpha subunit cleavage are inactive with a very low open probability. In contrast, channels lacking both alpha subunit cleavage and the tract alphaAsp-206-Arg-231 are active when expressed in oocytes, suggesting that alphaAsp-206-Arg-231 functions as an inhibitor that stabilizes the channel in the closed conformation. A synthetic 26-mer peptide (alpha-26), corresponding to alphaAsp-206-Arg-231, reversibly inhibits wild-type mouse ENaCs expressed in Xenopus oocytes, as well as endogenous Na(+) channels expressed in either a mouse collecting duct cell line or primary cultures of human airway epithelial cells. The IC(50) for amiloride block of ENaC was not affected by the presence of alpha-26, indicating that alpha-26 does not bind to or interact with the amiloride binding site. Substitution of Arg residues within alpha-26 with Glu, or substitution of Pro residues with Ala, significantly reduced the efficacy of alpha-26. The peptide inhibits ENaC by reducing channel open probability. Our results suggest that proteolysis of the alpha subunit activates ENaC by disassociating an inhibitory domain (alphaAsp-206-Arg-231) from its effector site within the channel complex.
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PMID:The epithelial Na+ channel is inhibited by a peptide derived from proteolytic processing of its alpha subunit. 1669 Jun 13

Epithelial sodium channels (ENaC) are processed by proteases as they transit the biosynthetic pathway. We recently observed that furin-dependent processing of the alpha-subunit of ENaC at two sites within its extracellular domain is required for channel activation due to release of a 26-residue inhibitory domain. While channels with alpha-subunits lacking the furin sites are not cleaved and have very low activity, channels lacking the furin consensus sites as well as the tract between these sites (alphaD206-R231) are active. We analyzed channels with a series of deletions in the tract alphaD206-R231 and lacking the alpha-subunit furin consensus sites in Xenopus laevis oocytes. We found an eight-residue tract that, when deleted, restored channel activity to the level found in oocytes expressing wild-type ENaC. A synthetic peptide, LPHPLQRL, representing the tract alphaL211-L218, inhibited wild-type ENaC expressed in oocytes with an IC(50) of 0.9 microM, and inhibited channels expressed in collecting duct cells and human primary airway epithelial cells with an IC(50)s of between approximately 50 and 100 microM. Analyses of peptides with deletions within this inhibitory tract indicate that eight residues is the minimal backbone length that is required for ENaC inhibition. Analyses of 8-mer peptides with conserved and nonconserved substitutions suggest that L(1), P(2), H(3), P(4), and L(8) are required for inhibitory activity. Our findings suggest that this eight-residue tract is a key conserved inhibitory domain that provides epithelial cells with a reserve of inactive channels that can be activated as required by proteases.
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PMID:Defining an inhibitory domain in the alpha-subunit of the epithelial sodium channel. 1803 49