Nω-Nitro-L-arginine: a potent inhibitor of the L-arginine-dependent soluble guanylate cyclase activation pathway in LLC-PK1 cells

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Abstract
Oxytocin increased cyclic GMP levels in LLC-PK1 porcine kidney epithelial cells through activation of soluble guanylate cyclase. NG-Monomethyl-L-arginine and Nω-nitro-L-arginine inhibited oxytocin (10 μM) induced cyclic GMP accumulation with IC50 values of 2.3 μM and 140 nM, respectively, and the inhibition was prevented with L-arginine. Both inhibitors at 100 μM lowered the basal levels of cyclic GMP, but did not affect those induced by 1 μM 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. Nω-Nitro-L-arginine is 16 times more potent than NG-monomethyl-L-arginine as a specific inhibitor of this pathway in LLC-PK1 cells.Key words: porcine kidney epithelial (LLC-PK1) cells, cyclic GMP, Nω-nitro-L-arginine, NG-monomethyl-L-arginine, endothelium-derived relaxing factor.