Linked Life Data

16164825

Source:http://linkedlifedata.com/resource/pubmed/id/16164825

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-9-16
pubmed:abstractText
Astrocytes have been recognized as important elements in controlling inflammatory as well as immune processes in the central nervous system (CNS). Recently, glial cells have been shown to produce cysteinyl leukotrienes (CysLTs) which are known lipid mediators of inflammation and whose extracellular concentrations rise under different pathological conditions in the brain. In the same conditions also extracellular concentrations of ATP dramatically increase reaching levels able to activate P2X7 ionotropic receptors for which an emerging role in neuroinflammation and neurodegeneration has been claimed. RTPCR analysis showed that primary cultures of rat brain astrocytes express P2X7 receptors. Application of the selective P2X7 agonist benzoyl benzoly ATP (BzATP) markedly increased [Ca2+]i which was mediated by a calcium influx from the extracellular milieu. The P2X7 antagonist, oATP, suppressed the BzATP-induced calcium increase. Consistent with the evidence that increased calcium levels activate the leukotriene biosynthetic pathway, challenge of astrocytes with either the calcium ionophore A23187 or BzATP significantly increased CysLT production and the cell pre-treatment with EGTA abolished these effects. Again the P2X7 antagonist prevented the BzATP-mediated CysLT efflux, whereas the astrocyte pretreatment with MK-571, a CysLT1 receptor antagonist, was ineffective. The astrocyte pre-treatment with a cocktail of inhibitors of ATP binding cassette (ABC) proteins reduced the BzATP-mediated CysLT production confirming that ABC transporters are involved in the release of CysLTs. The astrocyte P2X7- evoked rise of CysLT efflux was abolished in the presence of MK-886, an inhibitor of 5-lipoxygenase activating protein (FLAP) whose expression, along with that of 5-lipoxygenase (5-LO) was reported by Northern Blot analysis. The stimulation of P2X7 induced an up-regulation of FLAPmRNA that was reduced by the antagonist oATP. These data suggest that in rat brain cultured astrocytes P2X7ATP receptors may participate in the control of CysLT release thus further supporting a role for extracellular ATP as an integral component of the inflammatory brain response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2',3'-dialdehyde ATP, http://linkedlifedata.com/resource/pubmed/chemical/3'-O-(4-benzoyl)benzoyladenosine..., http://linkedlifedata.com/resource/pubmed/chemical/5-Lipoxygenase-Activating Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Affinity Labels, http://linkedlifedata.com/resource/pubmed/chemical/Alox5ap protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Chelating Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine, http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Indoles, http://linkedlifedata.com/resource/pubmed/chemical/Ionophores, http://linkedlifedata.com/resource/pubmed/chemical/L 663536, http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Leukotrienes, http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Propionates, http://linkedlifedata.com/resource/pubmed/chemical/Purinergic P2 Receptor Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Quinolines, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2, http://linkedlifedata.com/resource/pubmed/chemical/cysteinyl-leukotriene, http://linkedlifedata.com/resource/pubmed/chemical/verlukast
pubmed:status
MEDLINE
pubmed:issn
0394-6320
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
417-30
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16164825-5-Lipoxygenase-Activating Proteins, pubmed-meshheading:16164825-Adenosine Triphosphate, pubmed-meshheading:16164825-Affinity Labels, pubmed-meshheading:16164825-Animals, pubmed-meshheading:16164825-Astrocytes, pubmed-meshheading:16164825-Brain, pubmed-meshheading:16164825-Calcimycin, pubmed-meshheading:16164825-Carrier Proteins, pubmed-meshheading:16164825-Cells, Cultured, pubmed-meshheading:16164825-Cerebral Cortex, pubmed-meshheading:16164825-Chelating Agents, pubmed-meshheading:16164825-Cysteine, pubmed-meshheading:16164825-Dose-Response Relationship, Drug, pubmed-meshheading:16164825-Egtazic Acid, pubmed-meshheading:16164825-Indoles, pubmed-meshheading:16164825-Ionophores, pubmed-meshheading:16164825-Leukotriene Antagonists, pubmed-meshheading:16164825-Leukotrienes, pubmed-meshheading:16164825-Lipoxygenase Inhibitors, pubmed-meshheading:16164825-Membrane Proteins, pubmed-meshheading:16164825-Propionates, pubmed-meshheading:16164825-Purinergic P2 Receptor Antagonists, pubmed-meshheading:16164825-Quinolines, pubmed-meshheading:16164825-RNA, Messenger, pubmed-meshheading:16164825-Rats, pubmed-meshheading:16164825-Receptors, Purinergic P2, pubmed-meshheading:16164825-Up-Regulation
pubmed:articleTitle
P2X7 receptor activation in rat brain cultured astrocytes increases the biosynthetic release of cysteinyl leukotrienes.
pubmed:affiliation
Dept. of Biomedical Sciences, Section of Pharmacology and Toxicology, G. D'Annunzio University of Chieti, Medical School, Chieti, Italy. p.ballerini@dsb.unich.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't