Linked Life Data

10665827

Source:http://linkedlifedata.com/resource/pubmed/id/10665827

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-2-18
pubmed:abstractText
Previous studies in vitro have shown that NK3 receptors exist on primary afferent terminals in rat spinal cord and mediate potentiation of the depolarisation-evoked substance P (SP) release. In the present study we have investigated the role of the NK3 receptor-mediated SP release system in a model of inflammatory pain. Monoarthritis was induced in rats by unilateral injection of complete Freund's adjuvant (CFA); withdrawal latencies to a thermal stimulus were subsequently measured at various times following CFA. The CFA-treated paw displayed hyperalgesia as early as 4 h after CFA injection and hyperalgesia was maintained until day 4 but had disappeared by day 21. The thermal hyperalgesia was associated with an increase in basal SP release from spinal cord synaptosomes. The possible involvement of endogenous neurokinin B acting at NK3 receptors was tested by using SB 223412-A [(S)-(-)-N-(alpha-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carbo xamide hydrochloride], a novel, potent (Ki=30 nM) and selective (Ki>10,000 nM for NK1 and NK2 receptors), non-peptidic NK3 receptor antagonist. In vitro SB 223412-A antagonised the potentiation of SP release produced by senktide in spinal cord synaptosomes. Administered systemically to monoarthritic rats (50 mg/kg, p.o., b.i.d., for 4 days), the NK3 receptor antagonist SB 223412-A significantly reduced thermal hyperalgesia and normalised the basal release of SP from spinal cord synaptosomes. The data suggest that neurokinin B acting at NK3 receptors that mediate SP release within the spinal cord play a role in inflammation. These NK3 receptors may represent, therefore, appropriate targets in the therapy of inflammatory pain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
141-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
NK3 receptor blockade prevents hyperalgesia and the associated spinal cord substance P release in monoarthritic rats.
pubmed:affiliation
Department of Biology, SmithKline Beecham S.p.A., Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't