Metabolic mechanism of wakefulness (and hunger) and sleep (and satiety): Role of adenosine triphosphate and hypocretin and other peptides.

The concurrent background level of metabolic activity may control state of vigilance, promoting wakefulness (and hunger) when it is low, or sleep (and satiety) when it is high. In a series of experiments, we have shown that sleep is dependent on feeding, but only because of the metabolic consequences of food ingestion. These consequences are sensed by glioneuronal populations (at least in the rostromedial hypothalamus), which probably respond to channel-bound adenosine triphosphate/diphosphate turnover (ischymetric monitoring) rather than to the binding of such downstream molecules as adenosine and cytochrome c oxidase. This basic signal is communicated to the vigilance-controlling centers by a cascade of peptidic and nonpeptidic messengers-messengers that promote wakefulness and hunger, possibly via a hypometabolic action (as in the case of neuropeptide Y or hypocretins), or somnolence and satiety, possibly via a hypermetabolic action (as in the case of leptin or certain serotonergic agents).