title: N omega-nitro-L-arginine: a potent inhibitor of the L-arginine-dependent soluble guanylate cyclase activation pathway in LLC-PK1 cells.
abstract: Oxytocin increased cyclic GMP levels in LLC-PK1 porcine kidney epithelial cells through activation of soluble guanylate cyclase. NG-Monomethyl-L-arginine and N omega-nitro-L-arginine inhibited oxytocin (10 microM) induced cyclic GMP accumulation with IC50 values of 2.3 microM and 140 nM, respectively, and the inhibition was prevented with L-arginine. Both inhibitors at 100 microM lowered the basal levels of cyclic GMP, but did not affect those induced by 1 microM sodium nitroprusside and 100 nM atrial natriuretic factor. These data support our hypothesis that an endothelium-derived relaxing factor-like substance is formed as the endogenous activator of soluble guanylate cyclase in an L-arginine-dependent fashion in various cell types. N omega-Nitro-L-arginine is 16 times more potent than NG-monomethyl-L-arginine as a specific inhibitor of this pathway in LLC-PK1 cells.
authors.affiliation: Department of Pharmacology, Northwestern University Medical School, Chicago, IL.
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: J F
authors.initials: JF
authors.lastname: Kerwin
authors.forename: F
authors.initials: F
authors.lastname: Murad
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D019335:Nitroarginine; D010121:Oxytocin / Q000494:pharmacology
chemical_list: D019335:Nitroarginine; D010121:Oxytocin; D001120:Arginine; D006162:Guanylate Cyclase; D006152:Cyclic GMP