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Orexin/Hypocretin Signaling

  • Jyrki P. Kukkonen
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (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.

Keywords

Adenylyl cyclase Calcium Diacylglycerol lipase Endocannabinoid Gi Gq Gs Heterotrimeric G-protein Hypocretin K+ channel Na+/Ca2+-exchanger Non-selective cation channel Orexin OX1 receptor OX2 receptor Phospholipase A2 Phospholipase C Phospholipase D Protein kinase C 

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. 1.Biochemistry and Cell Biology, Department of Veterinary BiosciencesUniversity of HelsinkiHelsinkiFinland

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