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 injec ted into the lateral cerebral ventricle (LCV). This factor showed chem ical and functional characteristics similar to flavin adenine dinucleo tide (FAD). Therefore, the effect of FAD on neuronal NOS activity was examined. FAD caused at least 2-fold stimulation of NOS partially puri fied from rat brain. This effect was not simply due to formation of th e holoenzyme. Kinetic analyses showed that NOS exhibited negative coop erativity with L-arginine, its substrate, and FAD counteracted this ef fect. Furthermore, injection of FAD into the LCV reduced the blood pre ssure. These results suggest that FAD stimulates neuronal NOS by count eracting its negative cooperativity with L-arginine and also lowers th e blood pressure by activating NOS.