Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-8-27
pubmed:abstractText
Activation of microglia has been implicated in many neurological conditions including Alzheimer's disease and neuropathic pain. Recent studies provide evidence that P2X ATP receptors on the surface of microglia play a crucial role in initiation of inflammatory cascades. We investigated changes in surface P2X receptors in BV-2 murine microglial cells following their activation by pro-inflammatory bacterial lipopolysaccharides (LPS). mRNA analysis using RT-PCR confirmed the presence of P2X4 and P2X7 as the main P2X subunits. Application of ATP at low (< or =100 microM) and high (> or =1 mM) concentrations, as well as BzATP, activated inward currents in BV-2 cells. Current responses of P2X4 and P2X7 subtypes could be distinguished based on their respective sensitivity to the positive modulator ivermectin and to the antagonist Brilliant Blue G. Treatment of BV-2 cells with LPS leads to a transient increase in ivermectin-sensitive P2X4 currents, while dominant P2X7 currents remain largely unaffected. This increase in P2X4 function was concomitant with higher receptor protein expression, itself related to an upregulation of P2X4 mRNA levels that peaked at 48 h post-LPS treatment. Our data demonstrate that although LPS activation has a minor impact on P2X7 receptors that remain the major ionotropic ATP receptors in microglia, it specifically enhances responses to low ATP concentrations mediated by P2X4 receptors, highlighting the significant contribution of both subtypes to neuroinflammatory mechanisms and pathologies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
496-504
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Differential regulation of microglial P2X4 and P2X7 ATP receptors following LPS-induced activation.
pubmed:affiliation
Montreal Neurological Institute, Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't