Orexin signaling in recombinant neuron-like cells.

To assess the role of orexin receptor signaling in neuron-like cells, Neuro-2a murine neuroblastoma and PC12 human pheochromocytoma cells were stably transfected with human OX(1) or OX(2) receptors. Activation of both receptors strongly elevated cellular inositol phosphates and Ca(2+). A difference in the potency between orexin-A and -B was seen for OX(1), but not OX(2) receptors. Dependence of the orexin-mediated Ca(2+) response on extracellular Ca(2+) and the observed Ba(2+) influx indicate that in addition to phospholipase C, orexin receptors also may couple to similar non-voltage-gated Ca(2+) channels in neuronal cells as previously characterized in non-neuronal cells.