Stimulation of nitric oxide-cyclic GMP pathway by L-arginine increases the release of hepatic lipase from cultured rat hepatocytes.
The nitric oxide-cyclic GMP pathway is still undefined regarding regulation of the release of hepatic lipase (HTGL). It was found that L-arginine (Arg) stimulated the release of HTGL activity from rat hepatocytes in a time- and dose-dependent manner. L-Arg-stimulated release of HTGL activity was inhibited by N-monomethyl-L-Arg, which is a nitric oxide synthase inhibitor. L-Arg markedly increased the cyclic GMP content of hepatocytes in the presence of a cyclic GMP phosphodiesterase inhibitor. Zaprinast. The release of the enzyme activity was also suppressed by methylene blue (a guanyl cyclase inhibitor) and KT5823 (a cyclic GMP-dependent protein kinase inhibitor). These results suggest that the stimulation of nitric oxide synthesis by L-Arg increases the release of HTGL activity due to processes associated with the elevation of cyclic GMP level, probably through an activation of protein kinase.
2nd Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.
T
T
Morita
Y
Y
Shimada
H
H
Ueki
A
A
Kanagawa
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002227:Carbazoles; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles; D008049:Lipase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D051381:Rats; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D047428:Protein Kinase Inhibitors; C073601:KT 5823; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D008049:Lipase; D006152:Cyclic GMP; D008751:Methylene Blue