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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q#_5 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q#_4 http://www.w3.org/ns/prov#value Transport processes along the nephron are regulated in part by hormone stimulation of adenylyl cyclases mediated by the heterotrimeric G protein G(s). To assess the role of this pathway in the regulation of Na-K-2Cl cotransporter abundance in the renal thick ascending limb (TAL), we studied mice with heterozygous disruption of the Gnas gene, which codes for the alpha-subunit of G(s). Outer medullary G(s)alpha protein abundance (as assessed by semiquantitative immunoblotting) and glucagon-stimulated cAMP production were significantly reduced in the heterozygous G(s)alpha knockout mice (GSKO) relative to their wild-type (WT) littermates. Furthermore, Na-K-2Cl cotransporter protein abundance in the outer medulla was significantly reduced (band density, 48% of WT). In addition, GSKO mice had a significantly reduced (72% of WT) urinary osmolality in response to a single injection of 1-deamino-[8-D-arginine]vasopressin (DDAVP), a vasopressin analog. In contrast, outer medullary protein expression of the type 3 Na/H exchanger (NHE-3) or Tamm-Horsfall protein did not differ between the GSKO mice and their WT littermates. However, abundance of type VI adenylyl cyclase was markedly decreased in the outer medullas of GSKO mice, suggesting a novel feed-forward regulatory mechanism. We conclude that expression of the Na-K-2Cl cotransporter of the TAL is dependent on G(s)alpha-mediated hormone stimulation, most likely due to long-term changes in cellular cAMP levels. http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/10444578 http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/10444578 http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q#_4 http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q#pubinfo http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q http://purl.org/dc/terms/created 2014-07-03T14:29:48.003+02:00 http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAZRLQA3DVwHcfrPXk67AHrcQu4kDxKuxVptVmXpvUW9Q http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234