Although the precise signalling roles of nitric oxide (NO) in the nervous system are still controversial, few would dispute the fact that this labile molecule affects neuronal physiology. A lot of research has been devoted to discovering how NO influences brain function. However, few studies have addressed the ways in which this gas is inactivated. As NO is so unstable, its existence in the cellular milieu is thought to be intrinsically short; a corollary of this idea is that cells do not need an inactivation mechanism for such a short-lived molecule. Now Griffiths and Garthwaite have tested this assumption, and obtained evidence for a cellular sink that can shape NO levels.

The authors prepared cell suspensions from rat cerebella, and measured their effect on the level of NO released by different donors. The cells reduced the concentration of the gas independently of other mechanisms known to consume NO, such as reaction with oxygen or with superoxide ions. Moreover, if the cells were challenged with a constant source of NO, they could actually clamp its concentration for several minutes; if NO release continued, the sink became saturated and the gas concentration rose in parallel.

NO signalling involves the activation of guanylyl cyclase. Does the NO sink affect this activation? Griffiths and Garthwaite measured the production of cyclic GMP in response to different clamped concentrations of NO, and found that the amounts of gas necessary to stimulate cGMP production were readily produced, despite the sink. At the same time, the authors wondered whether the sink might help to prevent any toxic effects of NO, focusing on its known influence on mitochondrial respiration. They found that if the clamp was not saturated, oxygen consumption was normal, but as soon as NO exceeded the capacity of the sink, respiration was inhibited.

So cells can shape the levels of NO by means of a sink, the identity of which now needs to be established. Although this sink might have physiological and pathological relevance, the relationship between the NO concentrations measured in this study and those found in vivo is uncertain. It will therefore be necessary to embark on studies using more physiologically relevant systems to determine the actual role of this enigmatic sink in brain function.