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Reverse pharmacology of orexin: from an orphan GPCR to integrative physiology

Takeshi Sakurai1

  • 1Department of Pharmacology, Institute of Basic Medical Science, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. stakeshi@md.tsukuba.ac.jp

Regulatory Peptides
|December 29, 2004
PubMed

Insights

Orexins are crucial neuropeptides regulating energy balance and sleep-wake cycles. Their deficiency is linked to narcolepsy, highlighting their role in arousal and motivated behaviors like feeding.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Sleep Medicine

Background:

  • Orexins, peptide ligands for G-protein coupled receptors (GPCRs), regulate energy homeostasis.
  • Orexin deficiency is a key factor in narcolepsy, indicating their role in sleep-wake regulation.

Purpose of the Study:

  • To elucidate the role of orexins in integrating peripheral energy signals with central nervous system (CNS) mechanisms.
  • To explore the functional interactions of orexin neurons with feeding and arousal centers.

Main Methods:

  • Review of neuroanatomical connections of orexin-producing neurons.
  • Analysis of electrophysiological studies on orexin neuron regulation by humoral factors and neurotransmitters.

Main Results:

  • Orexin neurons interact with brainstem arousal centers and hypothalamic feeding centers.
  • Orexin neurons are modulated by peripheral signals like leptin, glucose, and ghrelin, as well as monoamines and acetylcholine.

Conclusions:

  • Orexin neurons serve as a critical link between peripheral energy balance and CNS control of sleep-wake states.
  • Orexin signaling influences motivated behaviors, including food seeking, by integrating metabolic and arousal cues.

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