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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-8
pubmed:abstractText
The human P2Y(13) receptor is a new receptor characterized by coupling to Gi, responsiveness to adenine di-phospho-nucleotides and blockade by the P2Y antagonist AR-C69931MX. The mouse P2Y(13) ortholog has also been reported. Here we report, for the first time, the cloning of rat P2Y(13) receptor, its pharmacological analysis and tissue distribution. Rat P2Y(13) is 79% and 87% identical to human and mouse P2Y(13) receptors, respectively. Expression of rP2Y(13) receptor in 1321N1 cells induced the appearance of responses to the typical P2Y(13) receptor agonists ADP and 2MeSADP, as detected by stimulation of [(35)S]GTPgammaS binding. Agonist activities were higher in cells transfected with rP2Y(13) receptor in the presence of the Galpha(16) subunit; in all cases agonist effects were abolished by pertussis toxin pre-treatment. At variance from both human and mouse receptors, ADP was more potent than 2MeSADP. Other nucleotides and sugar-nucleotides were ineffective. Both in the absence and presence of Galpha(16), activation of rP2Y(13) receptor by ADP and 2MeSADP was completely inhibited by nM concentrations of AR-C69931MX. In contrast, no inhibition of rP2Y(13) receptor was induced by the selective P2Y(1) receptor antagonist MRS2179. rP2Y(13) receptor showed highest expression levels in spleen, followed by liver and brain (with particularly high levels in cortex and striatum as reported in man), suggesting important roles in the nervous and immune systems. Expression levels comparable to those of the other cloned P2Y receptors were found in primary rat astrocytes, indicating a possible role in reactive astrogliosis. Hence, rat P2Y(13) receptor displays several similarities but also interesting differences with its human and mouse orthologs, that will have to be taken into account when characterizing the pathophysiological roles of this receptor in the rat animal models.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
113-24
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Cloning, pharmacological characterisation and distribution of the rat G-protein-coupled P2Y(13) receptor.
pubmed:affiliation
Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, Milan 20133, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't