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 regul ation of the release of hepatic lipase (HTGL). It was found that L-arg inine (Arg) stimulated the release of HTGL activity from rat hepatocyt es in a time- and dose-dependent manner. L-Arg-stimulated release of H TGL activity was inhibited by N-monomethyl-L-Arg, which is a nitric ox ide synthase inhibitor. L-Arg markedly increased the cyclic GMP conten t of hepatocytes in the presence of a cyclic GMP phosphodiesterase inh ibitor, zaprinast. The release of the enzyme activity was also suppres sed by methylene blue (a guanyl cyclase inhibitor) and KT5823 (a cycli c GMP-dependent protein kinase inhibitor). These results suggest that the stimulation of nitric oxide synthesis by L-Arg increases the relea se of HTGL activity due to processes associated with the elevation of cyclic GMP level, probably through an activation of protein kinase.