Document Detail

Orexins and appetite regulation.
MedLine Citation:
PMID:  12450737     Owner:  NLM     Status:  MEDLINE    
Initial research on the functional significance of two novel hypothalamic neuropeptides, orexin-A and orexin-B, suggested an important role in appetite regulation. Since then, however, these peptides have also been shown to influence a wide range of other physiological and behavioural processes. In this paper, we review the now quite extensive literature on orexins and appetite control, and consider their additional effects within this context. Although the evidence for orexin (particularly orexin-A and the orexin-1 receptor) involvement in many aspects of ingestive physiology and behaviour is incontrovertible, central administration of orexins is also associated with increased EEG arousal and wakefulness, locomotor activity and grooming, sympathetic and HPA activity, and pain thresholds. Since the orexin system is selectively activated by signals indicating severe nutritional depletion, it would be highly adaptive for a hungry animal not only to seek sustenance but also to remain fully alert to dangers in the environment. Crucial evidence indicates that orexin-A increases food intake by delaying the onset of a behaviourally normal satiety sequence. In contrast, a selective orexin-1 receptor antagonist (SB-334867) suppresses food intake and advances the onset of a normal satiety sequence. These data suggest that orexin-1 receptors mediate the episodic signalling of satiety and appear to bridge the transition from eating to resting in the rats' feeding-sleep cycle. The argument is developed that the diverse physiological and behavioural effects of orexins can best be understood in terms of an integrated set of reactions which function to rectify nutritional status without compromising personal survival. Indeed, many of the non-ingestive effects of orexin administration are identical to the cluster of active defences mediated via the lateral and dorsolateral columns of the midbrain periaqueductal gray matter, i.e., somatomotor activation, vigilance, tachycardia, hypertension and non-opioid analgesia. In our view, therefore, the LH orexin system is very well placed to orchestrate the diverse subsystems involved in foraging under potentially dangerous circumstances, i.e., finding and ingesting food without oneself becoming a meal for someone else.
R J Rodgers; Y Ishii; J C G Halford; J E Blundell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Neuropeptides     Volume:  36     ISSN:  0143-4179     ISO Abbreviation:  Neuropeptides     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-11-26     Completed Date:  2003-03-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8103156     Medline TA:  Neuropeptides     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  303-25     Citation Subset:  IM    
School of Psychology, University of Leeds, Leeds, UK.
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MeSH Terms
Appetite Regulation / drug effects,  physiology*
Blood Pressure / drug effects
Body Temperature / drug effects
Carrier Proteins / administration & dosage,  physiology*
Electroencephalography / drug effects
Feeding Behavior / drug effects,  physiology*
Grooming / drug effects
Heart Rate / drug effects
Hypothalamus / drug effects,  physiology*
Insulin / metabolism
Intracellular Signaling Peptides and Proteins*
Locomotion / drug effects
Neuropeptides / administration & dosage,  physiology*
Receptors, G-Protein-Coupled
Receptors, Neuropeptide / antagonists & inhibitors,  physiology*
Satiation / drug effects
Serotonin / metabolism
Wakefulness / drug effects
Reg. No./Substance:
0/Carrier Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/Receptors, G-Protein-Coupled; 0/Receptors, Neuropeptide; 0/orexin receptors; 0/orexins; 11061-68-0/Insulin; 50-67-9/Serotonin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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