Linked Life Data

16352704

Source:http://linkedlifedata.com/resource/pubmed/id/16352704

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-3-22
pubmed:abstractText
The hypothalamic peptides hypocretin-1 (orexin A) and -2 (orexin B) promote wakefulness by mechanisms that are not well understood. Defects in hypocretinergic neurotransmission underlie the human sleep disorder narcolepsy. Hypocretins alter cell excitability via two receptor subtypes, hypocretin receptor subtype 1 (hcrt-r1) and hypocretin receptor subtype 2 (hcrt-r2). This study aimed to identify G protein subtypes activated by hypocretin in rat pontine reticular nucleus oral part (PnO) and the hypocretin receptor subtype modulating acetylcholine (ACh) release in the PnO. G protein activation was quantified using in vitro [(35)S]guanylyl-5'-O-(gamma-thio)triphosphate autoradiography. ACh release was measured using in vivo microdialysis and high-performance liquid chromatography. Hypocretin-1-stimulated G protein activation was significantly decreased by pertussis toxin, demonstrating that some hypocretin receptors in rat PnO activate inhibitory G proteins. Hypocretin-1-stimulated ACh release was not blocked by pertussis toxin, supporting the conclusion that the hypocretin receptors modulating ACh release in rat PnO activate stimulatory G proteins. Hypocretin-1 and -2 each caused a concentration-dependent increase in ACh release with similar potencies, indicating that hcrt-r2 modulates ACh release in PnO. Hypocretin-1 caused a significantly greater increase in ACh release than hypocretin-2, suggesting a role for hcrt-r1 in the modulation of PnO ACh release. Taken together, these data provide the first evidence that hypocretin receptors in rat PnO signal via inhibitory and stimulatory G proteins and that ACh release in rat PnO is modulated by hcrt-r2 and hcrt-r1. One mechanism by which hypocretin promotes arousal may be to increase ACh release in the pontine reticular formation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
317
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
163-71
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Hypocretin (orexin) receptor subtypes differentially enhance acetylcholine release and activate g protein subtypes in rat pontine reticular formation.
pubmed:affiliation
Department of Anesthesiology, University of Michigan, Ann Arbor, 48109, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural