Evidence map›Paper›PMID 23902572›Full record

ReviewBritish journal of pharmacology2014

Orexin/hypocretin receptor signalling cascades.

J P Kukkonen, C S Leonard

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Narcolepsy is (not) an autoimmune disease.Nature reviews. Neurology · 2026
    Review
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  14. Non-canonical GScientific reports · 2025
    Article
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  17. Distinct Neuromodulatory Effects of Endogenous Orexin and Dynorphin Corelease on Projection-Defined Ventral Tegmental Dopamine Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  18. Article
  19. Article
  20. Article

26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

J P KukkonenBiochemistry and Cell Biology, Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
C S Leonard
New York Medical College · USUniversity of Helsinki · FI

Funding

"Synaptic Modulation of Mesopontine Cholingergic Neurons"R01NS027881 · NINDS · NEW YORK UNIVERSITY · PI LEONARD, CHRISTOPHER S · 1992 to 2022
$7.1M
K+-CHANNELS REGULATING REM-RELATED CHOLINGERGIC NEURONSR01HL064150 · NHLBI · NEW YORK MEDICAL COLLEGE · PI LEONARD, CHRISTOPHER S · 1999 to 2011
$2.6M
NHLBI NIH HHS R01 HL064150NINDS NIH HHS R01 NS027881
6 · The paper itself

Abstract

Orexin (hypocretin) peptides and their two known G-protein-coupled receptors play essential roles in sleep-wake control and powerfully influence other systems regulating appetite/metabolism, stress and reward. Consequently, drugs that influence signalling by these receptors may provide novel therapeutic opportunities for treating sleep disorders, obesity and addiction. It is therefore critical to understand how these receptors operate, the nature of the signalling cascades they engage and their physiological targets. In this review, we evaluate what is currently known about orexin receptor signalling cascades, while a sister review (Leonard & Kukkonen, this issue) focuses on tissue-specific responses. The evidence suggests that orexin receptor signalling is multifaceted and is substantially more diverse than originally thought. Indeed, orexin receptors are able to couple to members of at least three G-protein families and possibly other proteins, through which they regulate non-selective cation channels, phospholipases, adenylyl cyclase, and protein and lipid kinases. In the central nervous system, orexin receptors produce neuroexcitation by postsynaptic depolarization via activation of non-selective cation channels, inhibition of K⁺ channels and activation of Na⁺/Ca²⁺ exchange, but they also can stimulate the release of neurotransmitters by presynaptic actions and modulate synaptic plasticity. Ca²⁺ signalling is also prominently influenced by these receptors, both via the classical phospholipase C-Ca²⁺ release pathway and via Ca²⁺ influx, mediated by several pathways. Upon longer-lasting stimulation, plastic effects are observed in some cell types, while others, especially cancer cells, are stimulated to die. Thus, orexin receptor signals appear highly tunable, depending on the milieu in which they are operating.

Indexed as

Amino Acid SequenceAnimalsCell DeathEndocannabinoidsGTP-Binding ProteinsHumansMolecular Sequence DataNeuronal PlasticityOrexin ReceptorsReceptors, G-Protein-CoupledSignal TransductionSynapsesEndocannabinoidsGTP-Binding ProteinsOrexin ReceptorsReceptors, G-Protein-Coupledadenylyl cyclasecell deathendocannabinoidG-protein-coupled receptorintracellular Ca2+K+ channelNa+/K+ exchangernon-selective cation channelphospholipaseplasticity

Identifiers

PMID23902572
PMCPMC3904254
OpenAlexW2098228975

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.