Serotonin binds to purified neuronal nitric oxide synthase: A possible explanation for ROS production induced by 5HT in the presence of nNOS

Serotonin (5HT) was shown to induce in vitro the production of ROS in the presence of neuronal nitric oxide synthase (nNOS) in addition to the basal NO formation. With the aim of understanding this mechanism, this study investigated the potential binding of 5HT to nNOS. By using [3H]5HT, it is reported here that 5HT binds to nNOS, but only when the enzyme is active and in a superoxide-dependent manner. This binding is prevented by DPI but not by L-NAME. The formation of 5HT-nNOS complex was shown to be very well correlated with the production of ROS by 5HT in the presence of nNOS. A mechanism involving nNOS only in its initial step is proposed to explain both the formation of 5HT-nNOS complex and the production of ROS observed in the presence of nNOS and 5HT.