Linked Life Data

16831297

Source:http://linkedlifedata.com/resource/pubmed/id/16831297

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-7-11
pubmed:abstractText
Among P2 metabotropic ATP receptors, P2Y2 subtype seems to be peculiar as its upregulation triggers important biological events in different cells types. In non-stimulated cells including astrocytes, P2Y2 receptors are usually expressed at levels lower than P2Y1 sites, however the promoter region of the P2Y2 receptors has not yet been studied and little is known about the mechanisms underlying the regulation of the expression of this ATP receptor. We showed that not only UTP and ATP are the most potent and naturally occurring agonist for P2Y2 sites, but also guanosine induced an up-regulation of astrocyte P2Y2 receptor mRNA evaluated by Northern blot analysis. We also focused our attention on this nucleoside since in our previous studies it was reported to be released by cultured astrocytes and to exert different neuroprotective effects. UTP and guanosine-evoked P2Y2 receptor up-regulation in rat brain cultured astrocytes was linked to an increased P2Y2-mediated intracellular calcium response, thus suggesting an increased P2Y2 activity. Actinomycin D, a RNA polymerase inhibitor, abrogated both UTP and guanosine-mediated P2Y2 up-regulation, thus indicating that de novo transcription was required. The effect of UTP and guanosine was also evaluated in astrocytes pretreated with different inhibitors of signal transduction pathways including ERK, PKC and PKA reported to be involved in the regulation of other cell surface receptor mRNAs. The results show that ERK1-2/MAPK pathway play a key role in the P2Y2 receptor up-regulation mediated by either UTP or guanosine. Moreover, our data suggest that PKA is also involved in guanosine-induced transcriptional activation of P2Y2 mRNA and that increased intracellular calcium levels and PKC activation may also mediate P2Y2 receptor up-regulation triggered by UTP. The extracellular release of ATP under physiological and pathological conditions has been widely studied. On the contrary, little is known about the release of pyrimidines and in particular of UTP. Here we show that astrocytes are able to release UTP, either at rest or during and following hypoxia/hypoglycemia obtained by submitting the cells to glucose-oxygen deprivation (OGD). Interestingly, also P2Y2 receptor mRNA increased by about two-fold the control values when the cultures were submitted to OGD. It has been recently reported that P2Y2 receptors can play a protective role in astrocytes, thus either guanosine administration or increased extracellular concentrations of guanosine and UTP reached locally following CNS injury may increase P2Y2-mediated biological events aimed at promoting a protective astrocyte response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0394-6320
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
293-308
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16831297-Adenosine Triphosphate, pubmed-meshheading:16831297-Animals, pubmed-meshheading:16831297-Astrocytes, pubmed-meshheading:16831297-Blotting, Northern, pubmed-meshheading:16831297-Brain, pubmed-meshheading:16831297-Brain Chemistry, pubmed-meshheading:16831297-Calcium, pubmed-meshheading:16831297-Cell Hypoxia, pubmed-meshheading:16831297-Cell Survival, pubmed-meshheading:16831297-Cells, Cultured, pubmed-meshheading:16831297-Chromatography, High Pressure Liquid, pubmed-meshheading:16831297-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16831297-Extracellular Space, pubmed-meshheading:16831297-Glucose, pubmed-meshheading:16831297-Guanosine, pubmed-meshheading:16831297-Pyrimidines, pubmed-meshheading:16831297-RNA, pubmed-meshheading:16831297-Rats, pubmed-meshheading:16831297-Receptors, Purinergic P2, pubmed-meshheading:16831297-Receptors, Purinergic P2Y2, pubmed-meshheading:16831297-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16831297-Signal Transduction, pubmed-meshheading:16831297-Stroke, pubmed-meshheading:16831297-Up-Regulation, pubmed-meshheading:16831297-Uridine Triphosphate
pubmed:articleTitle
P2Y2 receptor up-regulation induced by guanosine or UTP in rat brain cultured astrocytes.
pubmed:affiliation
Dept. of Biomedical Sciences, Section of Pharmacology and Toxicology, Medical School, University G. D'Annunzio of Chieti-Pescara, Via dei Vestini 29, 66013 Chieti, Italy. p.ballerini@dsb.unich.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't