ACTIVATION OF NEURONAL NITRIC-OXIDE SYNTHASE BY FLAVIN ADENINE-DINUCLEOTIDE

Bovine adrenals were found to contain a factor that activates neuronal nitric oxide synthase (NOS) and reduces the blood pressure when injected into the lateral cerebral ventricle (LCV). This factor showed chemical and functional characteristics similar to flavin adenine dinucleotide (FAD). Therefore, the effect of FAD on neuronal NOS activity was examined. FAD caused at least 2-fold stimulation of NOS partially purified from rat brain. This effect was not simply due to formation of the holoenzyme. Kinetic analyses showed that NOS exhibited negative cooperativity with L-arginine, its substrate, and FAD counteracted this effect. Furthermore, injection of FAD into the LCV reduced the blood pressure. These results suggest that FAD stimulates neuronal NOS by counteracting its negative cooperativity with L-arginine and also lowers the blood pressure by activating NOS.