抄録
Ghrelin is produced in some peripheral organs and brain, and acts as a stimulator for growth hormone (GH) secretion and food intake via GH secretagogue receptors (GHS-Rs). Recent studies further suggest that ghrelin participates in the regulation of sleep-wakefulness. Pedunculopontine tegmental nucleus (PPT), which is one of brain sites that control sleep-wakefulness, also expresses GHS-Rs. However, the action of ghrelin on PPT neurons is remained unclear. Thus, we examined the effects of ghrelin on PPT neurons using rat brain slice preparations and whole-cell patch clamp recording technique. Bath-application of ghrelin depolarized PPT neurons, and the depolarization persisted in the presence of tetrodotoxin. The ghrelin-induced depolarization was accompanied by increase of membrane resistance. When extracellular K+ concentration was increased or extracellular Na+ was replaced by N-methyl-D-glucamine+ (NMDG+), the ghrelin-induced depolarization significantly decreased, but did not disappear. However, when external solution was modified together with the increase of extracellular K+ and the replacement of extracellular Na+ with NMDG+, the depolarization disappeared completely. These results suggest that ghrelin depolarizes PPT neurons via closing of K+ channels and activating of external Na+ influx pathway, and participates in the regulation of sleep-wakefulness through the excitatory effects on PPT neurons. [J Physiol Sci. 2008;58 Suppl:S95]
