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Behavioral Neuroscience of Orexin/Hypocretin pp 17–50Cite as

Orexin/Hypocretin Signaling

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Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 33))

Abstract

Orexin/hypocretin peptide (orexin-A and orexin-B) signaling is believed to take place via the two G-protein-coupled receptors (GPCRs), named OX1 and OX2 orexin receptors, as described in the previous chapters. Signaling of orexin peptides has been investigated in diverse endogenously orexin receptor-expressing cells – mainly neurons but also other types of cells – and in recombinant cells expressing the receptors in a heterologous manner. Findings in the different systems are partially convergent but also indicate cellular background-specific signaling. The general picture suggests an inherently high degree of diversity in orexin receptor signaling.

In the current chapter, I present orexin signaling on the cellular and molecular levels. Discussion of the connection to (potential) physiological orexin responses is only brief since these are in focus of other chapters in this book. The same goes for the post-synaptic signaling mechanisms, which are dealt with in Burdakov: Postsynaptic actions of orexin. The current chapter is organized according to the tissue type, starting from the central nervous system. Finally, receptor signaling pathways are discussed across tissues, cell types, and even species.

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Abbreviations

2-AG:

2-Arachidonoyl glycerol

σ1:

Sigma 1 receptor

κOR:

κ Opioid receptor

AC:

Adenylyl cyclase

ACTH:

Adrenocorticotropic hormone

BRET and FRET:

Bioluminescence and fluorescence/Förster resonance energy transfer, respectively

CHO:

Chinese hamster ovary (cells)

CNS:

Central nervous system

CRF and CRF1:

Corticotropin-releasing factor and corticotropin-releasing factor receptor 1, respectively

DAG:

Diacylglycerol

ER:

Endoplasmic reticulum

GEF:

Guanine nucleotide exchange factor

GPCR:

G-protein-coupled receptor

Gαβγ, Gα and Gβγ:

Heterotrimeric G-protein heterotrimeric complex, α-subunit, and the βγ-subunit complex, respectively

IP3:

Inositol-1,4,5-trisphosphate

JNK:

c-Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

MEF:

Mouse embryonic fibroblast

mTORC1:

Mammalian target of rapamycin complex 1

NCX:

Na+/Ca2+-exchanger

NSCC:

Non-selective cation channel

p70S6K:

p70 ribosomal S6 kinase

p90RSK:

p90 ribosomal S6 kinase

PI3K:

Phosphoinositide-3-kinase

PIP2:

Phosphatidylinositol-4,5-bisphosphate

PKA, PKB, and PKC:

Protein kinase A, B, and C, respectively

PLA2, PLC, and PLD:

Phospholipase A2, C, and D, respectively

PP5:

Protein phosphatase 5

TRP:

Transient receptor potential (channel)

VTA:

Ventral tegmental area

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Authors and Affiliations

  1. Biochemistry and Cell Biology, Department of Veterinary Biosciences, University of Helsinki, POB 66, FIN-00014, Helsinki, Finland

    Jyrki P. Kukkonen

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  1. Jyrki P. Kukkonen
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Correspondence to Jyrki P. Kukkonen .

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  1. Florey Institute of Neuroscience & Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia

    Andrew J Lawrence

  2. Dep Psychiatry & Behav Sciences, Stanford University, Stanford, CA, USA

    Luis de Lecea

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Kukkonen, J.P. (2016). Orexin/Hypocretin Signaling. In: Lawrence, A.J., de Lecea, L. (eds) Behavioral Neuroscience of Orexin/Hypocretin. Current Topics in Behavioral Neurosciences, vol 33. Springer, Cham. https://doi.org/10.1007/7854_2016_49

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