Orexin-A and ghrelin depolarize the same pedunculopontine tegmental neurons in rats: An in vitro study

Orexin (ORX), also called hypocretin, and ghrelin are newly identified peptides in the brain and/or peripheral organs, and they are involved in the regulation of sleep–wakefulness as well as feeding. In our previous studies we have found that ORX and ghrelin each depolarizes more than half of the cholinergic neurons recorded in the pedunculopontine tegmental nucleus (PPT) via a dual ionic mechanism including a decrease of K+ conductance and an increase of nonselective cationic conductance. Thus, the present study was carried out to investigate whether ORX-A and ghrelin both depolarize the same PPT neuron. About 60% of PPT neurons examined was depolarized by both ORX-A and ghrelin, 20% by ORX-A alone, and 10% by ghrelin alone. The remaining 10% did not respond to these peptides. In neurons which were responsive to both ORX-A and ghrelin, the depolarizations induced by ORX-A and ghrelin were additive. In addition, the ORX-A- and ghrelin-induced depolarizations were both blocked by D609, a phosphatidylcholine-specific phospholipase C (PLC) inhibitor. These results suggest that same PPT neurons with receptors for ORX and ghrelin are involved in the cellular process through which ORX and ghrelin participate in the regulation of sleep wakefulness, and that the excitatory effects of ORX and ghrelin on PPT neurons are mediated by PLC.