Neurons that say NO

Thirty years ago, Thomas and Pearse discovered what they termed 'solitary active cells'--neurons containing an unusually high nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) activity that could be detected histochemically. Although these neurons were considered as something special, an appropriate mechanism to account for their outstanding metabolism was not provided until the recent identification of neuronal NADPH-diaphorase as nitric oxide synthase. This simple histochemical method now allows the precise anatomical localization of the neurons generating the exotic messenger molecule nitric oxide. This article reviews the functional implications that arise from our new knowledge of the anatomy of the nitric oxide signal transduction pathway in the nervous system. The widespread distribution of this system indicates that for those interested in cellular communication nitric oxide is a gas to study.