Linked Life Data

8913350

Source:http://linkedlifedata.com/resource/pubmed/id/8913350

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1996-12-26
pubmed:abstractText
Dilute formalin injected into the rat hindpaw as a nociceptive stimulus increases neurokinin-1 receptor (NK-1R) mRNA levels in the dorsal horn of the spinal cord. Increased NK-1R mRNA levels could result from increased mRNA stability or an increased rate of NK-1R mRNA transcription. In this study, RNA samples prepared from the spinal cords of rats receiving an injection of formalin into the right hindpaw were assayed for NK-1R mRNA with the use of solution hybridization-nuclease protection assays. The mature and incompletely spliced NK-1R-encoding RNAs protected by endogenous rat RNAs were characterized by the use of NK-1R plasmid constructs containing intron sequences. NK-1R pre-mRNA species were enriched in the nuclear fractions of spinal cord samples, and in the steady state, total molar amounts of NK-1R pre-mRNAs were 2-fold greater than those of mature NK-1R mRNA. In formalin-treated animals, the temporal pattern of peak pre-mRNA levels compared with mature mRNA indicated that chemogenic nociception either activates transcription of the NK-1R gene or decreases the rate of pre-mRNA splicing. In the ipsilateral lumbar dorsal hom, NK-1R mRNA levels were significantly increased at 2 and 6 hr after formalin injection. Levels of the NK-1R pre-mRNA containing both introns A and B were significantly increased 1 hr after formalin treatment, and levels of NK-1R pre-mRNAs containing intron A were significantly elevated at 2 hr after formalin treatment. Pretreatment of rats with the selective NK-1R antagonist LY306,740 was used to determine the role of NK-1R activation in the regulation of nociception-induced NK-1R mRNA levels. Rats were pretreated with either LY306,740 or LY307,679 (an inactive enantiomer) before injection of formalin into the right hindpaw. Pretreatment with LY306,740 (but not LY307,679) completely blocked the formalin-induced increase in dorsal horn NK-1R mRNA levels and significantly reduced formalin-induced behavioral activity. Thus, activation of the NK-1R during nociception increases dorsal horn NK-1R mRNA levels through activation of transcriptional or splicing mechanisms. The stimulation of NK-1R gene expression by activation of the NK-1R provides a homologous mechanism for altering the sensitivity of dorsal horn cells to substance P, potentially via the actions of second messengers, which presumably results in the maintenance of proper sensory information processing during long term nociception.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1189-99
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
The neurokinin-1 receptor antagonist LY306,740 blocks nociception-induced increases in dorsal horn neurokinin-1 receptor gene expression.
pubmed:affiliation
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.