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 pathophysiology of brain cell function. Because of their labile nature, however, it has been difficult to investigate their actions directly. This problem has been addressed, in primary rat brain cell cultures, in this study by utilization of two novel electrochemical sensors. It has been demonstrated that extracellular superoxide originates from the astrocytic subpopulation in a calcium/calmodulin dependent manner and responds to constitutive nitric oxide synthase inhibition. The results indicate a novel function for the astrocytic constitutive nitric oxide synthase in regulating extracellular superoxide release and, therefore, controlling neuronal nitric oxide availability.