RGD Reference Report - Orexin receptor type-1 couples exclusively to pertussis toxin-insensitive G-proteins, while orexin receptor type-2 couples to both pertussis toxin-sensitive and -insensitive G-proteins. - Rat Genome Database

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Orexin receptor type-1 couples exclusively to pertussis toxin-insensitive G-proteins, while orexin receptor type-2 couples to both pertussis toxin-sensitive and -insensitive G-proteins.

Authors: Zhu, Y  Miwa, Y  Yamanaka, A  Yada, T  Shibahara, M  Abe, Y  Sakurai, T  Goto, K 
Citation: Zhu Y, etal., J Pharmacol Sci. 2003 Jul;92(3):259-66.
RGD ID: 1642020
Pubmed: PMID:12890892   (View Abstract at PubMed)

Signal transduction pathways of orexin receptors were examined using a nerve-like cell line transfected with orexin receptor type-1 (OX1R) and orexin receptor type-2 (OX2R). Forskolin-stimulated cyclic adenosine 3,5-monophosphate (cAMP) accumulation in OX2R-expressing cells was inhibited by orexin in a dose-dependent manner, and the effect was abolished by pretreatment with pertussis toxin (PTX). The inhibitory effect of orexin on forskolin-stimulated cAMP accumulation was not observed in OX1R-expressing cells. Administration of orexin to these cells resulted in a transient increase of intracellular calcium concentration ([Ca(2+)](i)). Orexin-stimulated increases in [Ca(2+)](i) in OX1R- or OX2R-expressing cells were not affected by the PTX pretreatment. These observations suggest that OX1R couples exclusively to PTX-insensitive G-proteins, while OX2R couples to both PTX-sensitive and -insensitive G-proteins. To examine the relative contributions of these G-proteins in OX2R-mediated activation of neurons, we used histaminergic tuberomammillary nucleus neurons, in which OX2R is abundantly expressed. We found that a phospholipase C (PLC)-inhibitor, U73122, inhibits orexin-mediated neuronal activation, but PTX showed no effect on it. This suggests that although OX2R couples to multiple G-proteins, activation of neurons by orexins through OX2R is mediated via a PTX-insensitive, PLC dependent pathway.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hcrtr1RatG protein-coupled receptor signaling pathway  IDA  RGD 
Hcrtr2RatG protein-coupled receptor signaling pathway  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hcrtr1Ratorexin receptor activity  IDA  RGD 
Hcrtr2Ratorexin receptor activity  IDA  RGD 
Hcrtr1Ratpeptide hormone binding  IDA  RGD 
Hcrtr2Ratpeptide hormone binding  IDA  RGD 
HcrtRattype 1 orexin receptor binding  IDA  RGD 
HcrtRattype 2 orexin receptor binding  IDA  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GNAI1HumanG protein mediated signaling pathway via Galphai family  ISOGnai1 (Rattus norvegicus) RGD 
Gnai1RatG protein mediated signaling pathway via Galphai family  IMP  RGD 
Gnai1MouseG protein mediated signaling pathway via Galphai family  ISOGnai1 (Rattus norvegicus) RGD 
HCRTR2HumanG protein mediated signaling pathway via Galphai family  ISOHcrtr2 (Rattus norvegicus) RGD 
Hcrtr2RatG protein mediated signaling pathway via Galphai family  IDA  RGD 
Hcrtr2MouseG protein mediated signaling pathway via Galphai family  ISOHcrtr2 (Rattus norvegicus) RGD 
GNAQHumanG protein mediated signaling pathway via Galphaq family  ISOGnaq (Rattus norvegicus) RGD 
GnaqRatG protein mediated signaling pathway via Galphaq family  IMP  RGD 
GnaqMouseG protein mediated signaling pathway via Galphaq family  ISOGnaq (Rattus norvegicus) RGD 
HCRTR1HumanG protein mediated signaling pathway via Galphaq family  ISOHcrtr1 (Rattus norvegicus) RGD 
HCRTR2HumanG protein mediated signaling pathway via Galphaq family  ISOHcrtr2 (Rattus norvegicus) RGD 
Hcrtr1MouseG protein mediated signaling pathway via Galphaq family  ISOHcrtr1 (Rattus norvegicus) RGD 
Hcrtr1RatG protein mediated signaling pathway via Galphaq family  IDA  RGD 
Hcrtr2RatG protein mediated signaling pathway via Galphaq family  IDA  RGD 
Hcrtr2MouseG protein mediated signaling pathway via Galphaq family  ISOHcrtr2 (Rattus norvegicus) RGD 
GnaqRatorexin/hypocretin signaling pathway via orexin/hypocretin receptor 1  IMP  RGD 
HCRTHumanorexin/hypocretin signaling pathway via orexin/hypocretin receptor 1  ISOHcrt (Rattus norvegicus) RGD 
HCRTR1Humanorexin/hypocretin signaling pathway via orexin/hypocretin receptor 1  ISOHcrtr1 (Rattus norvegicus) RGD 
HcrtMouseorexin/hypocretin signaling pathway via orexin/hypocretin receptor 1  ISOHcrt (Rattus norvegicus) RGD 
HcrtRatorexin/hypocretin signaling pathway via orexin/hypocretin receptor 1  IDA  RGD 
Hcrtr1Mouseorexin/hypocretin signaling pathway via orexin/hypocretin receptor 1  ISOHcrtr1 (Rattus norvegicus) RGD 
Hcrtr1Ratorexin/hypocretin signaling pathway via orexin/hypocretin receptor 1  IDA  RGD 
Gnai1Ratorexin/hypocretin signaling pathway via orexin/hypocretin receptor 2  IMP  RGD 
GnaqRatorexin/hypocretin signaling pathway via orexin/hypocretin receptor 2  IMP  RGD 
HCRTHumanorexin/hypocretin signaling pathway via orexin/hypocretin receptor 2  ISOHcrt (Rattus norvegicus) RGD 
HCRTR2Humanorexin/hypocretin signaling pathway via orexin/hypocretin receptor 2  ISOHcrtr2 (Rattus norvegicus) RGD 
HcrtMouseorexin/hypocretin signaling pathway via orexin/hypocretin receptor 2  ISOHcrt (Rattus norvegicus) RGD 
HcrtRatorexin/hypocretin signaling pathway via orexin/hypocretin receptor 2  IDA  RGD 
Hcrtr2Ratorexin/hypocretin signaling pathway via orexin/hypocretin receptor 2  IDA  RGD 
Hcrtr2Mouseorexin/hypocretin signaling pathway via orexin/hypocretin receptor 2  ISOHcrtr2 (Rattus norvegicus) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Gnai1  (G protein subunit alpha i1)
Gnaq  (G protein subunit alpha q)
Hcrt  (hypocretin neuropeptide precursor)
Hcrtr1  (hypocretin receptor 1)
Hcrtr2  (hypocretin receptor 2)

Genes (Mus musculus)
Gnai1  (G protein subunit alpha i1)
Gnaq  (guanine nucleotide binding protein, alpha q polypeptide)
Hcrt  (hypocretin)
Hcrtr1  (hypocretin (orexin) receptor 1)
Hcrtr2  (hypocretin (orexin) receptor 2)

Genes (Homo sapiens)
GNAI1  (G protein subunit alpha i1)
GNAQ  (G protein subunit alpha q)
HCRT  (hypocretin neuropeptide precursor)
HCRTR1  (hypocretin receptor 1)
HCRTR2  (hypocretin receptor 2)


Additional Information