Release of Lipoprotein Lipase Induced by L-Arginine in Mouse Mammary Tumor FM3A Cells

Abstract

The nitric oxide (NO)/cyclic guanosine 5'-monophosphate (GMP) pathway remains undefined regarding the regulation of lipoprotein lipase (LPL) release. Here, we investigated whether L-arginine (Arg) stimulates the release of LPL from mouse mammary tumor FM3A cells in a time- and dose-dependent manner. L-Arg-stimulated release of LPL activity was inhibited by N^G-monomethyl-L-Arg monoacetate, which is an endothelial NO synthase (NOS) inhibitor. Furthermore, release of enzyme activity was also suppressed by various inhibitors of guanylate cyclase and adenylate cyclase, as well as cyclic GMP- and cyclic adenosine 5'-monophosphate (AMP)-dependent protein kinases (PKG and PKA). L-Arg also increased intracellular cyclic GMP contents as well as intracellular cyclic AMP contents. In addition, the increase in the cyclic AMP contents was reduced by inhibitors of guanylate cyclase and PKG. These results suggest that the stimulatory release of LPL from tumor cells by L-Arg is partly due to activation of cyclic AMP production and PKA activity caused by elevated cyclic GMP production and PKG activity.