title: Cellular distribution and function of soluble guanylyl cyclase in rat kidney and liver.
abstract: Soluble guanylyl cyclase (sGC) catalyzes the biosynthesis of cGMP in response to binding of L-arginine-derived nitric oxide (NO). Functionally, the NO-sGC-cGMP signaling pathway in kidney and liver has been associated with regional hemodynamics and the regulation of glomerular parameters. The distribution of the ubiquitous sGC isoform alpha 1 beta 1 sGC was studied with a novel, highly specific antibody against the beta 1 subunit. In parallel, the presence of mRNA encoding both subunits was investigated by using in situ hybridization and reverse transcription-PCR assays. The NO-induced, sGC-dependent accumulation of cGMP in cytosolic extracts of tissues and cells was measured in vitro. Renal glomerular arterioles, including the renin-producing granular cells, mesangium, and descending vasa recta, as well as cortical and medullary interstitial fibroblasts, expressed sGC. Stimulation of isolated mesangial cells, renal fibroblasts, and hepatic Ito cells with a NO donor resulted in markedly increased cytosolic cGMP levels. This assessment of sGC expression and activity in vascular and interstitial cells of kidney and liver may have implications for understanding the role of local cGMP signaling cascades.
authors.affiliation: Department of Anatomy, Charité, Humboldt University, Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Theilig
authors.affiliation: Department of Anatomy, Charité, Humboldt University, Berlin, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bostanjoglo
authors.affiliation: Department of Nephrology, University of Freiburg, Freiburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.affiliation: Department of Nephrology, University of Göttingen, Göttingen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Grupp
authors.affiliation: Department of Anatomy, Charité, Humboldt University, Berlin, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Holland
authors.affiliation: Department of Anatomy, Charité, Humboldt University, Berlin, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Slosarek
authors.affiliation: Department of Clinical Chemistry, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
authors.forename: Axel M
authors.initials: AM
authors.lastname: Gressner
authors.affiliation: Department of Pharmacology, Ruhr University, Bochum, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Russwurm
authors.affiliation: Department of Pharmacology, Ruhr University, Bochum, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Koesling
authors.affiliation: Department of Anatomy, Charité, Humboldt University, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006162:Guanylate Cyclase / Q000737:chemistry / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000201:enzymology*; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D009569:Nitric Oxide; D006162:Guanylate Cyclase