Superoxide generation from constitutive nitric oxide synthase in astrocytes in vitro regulates extracellular nitric oxide availability

Oxygen-derived free radicals play an important role in the physiology and p athophysiology of brain cell function. Because of their labile nature, howe ver, it has been difficult to investigate their actions directly. This prob lem has been addressed, in primary rat brain cell cultures, in this study b y utilization of two novel electrochemical sensors. It has been demonstrate d that extracellular superoxide originates from the astrocytic subpopulatio n in a calcium/calmodulin dependent manner and responds to constitutive nit ric oxide synthase inhibition. The results indicate a novel function for th e astrocytic constitutive nitric oxide synthase in regulating extracellular superoxide release and, therefore, controlling neuronal nitric oxide avail ability. (C) 1998 Elsevier Science Inc.