MODULATION OF HEME OXYGENASE ACTIVITY IN RAT-BRAIN AND SPLEEN BY INHIBITORS AND DONORS OF NITRIC-OXIDE

The capacity of nitric oxide to activate or inhibit metalloprotein-containing enzymes underlies many of its biological actions. Heme oxygenase, involved in a variety of biological processes, does not contain heme but utilises it as a substrate. The substrate for nitric oxide, L-arginine (0.1-10mM), but not D-arginine, decreased heme oxygenase activity in rat brain homogenates. The arginine analogue L-NAME (0.1-10mM) increased activity in the same tissue. In spleen homogenates where endogenous nitric oxide activity is lower than in brain, these compounds had no effect. The nitric oxide donor sodium nitroprusside (0.001mM-10mM) reduced heme oxygenase activity in both brain and spleen. These results suggest that biological effects attributed to modulation of nitric oxide synthase may act via heme oxygenase. (C) 1995 Academic Press, Inc.