Linked Life Data

11864978

Source:http://linkedlifedata.com/resource/pubmed/id/11864978

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2002-4-29
pubmed:abstractText
Although P2X receptors are suggested to play a role in synaptic neurotransmission, the specific physiological role of each P2X receptor subtype remains largely unknown. We used cultured chick embryo ventricular myocytes as a model to study a potential physiological role of the P2X(4) receptor in mediating the positive inotropic effect of ATP. The chick P2X4 receptor (cP2X(4)R) mRNA was expressed in the heart and the pharmacological features of the ATP-induced positive inotropic response were similar to those of the cP2X(4)R in terms of insensitivity to blockade by known P2 receptor antagonists and the ineffectiveness of adenosine 5'-(alpha,beta-methylene)triphosphate as an agonist. Treatment of myocytes with antisense oligonucleotides specific to the 5' region of cP2X(4)R abrogated the P2 agonist-stimulated (45)Ca influx. Similarly, antisense oligonucleotide treatment also blocked the 2-methylthio-ATP-stimulated increase in contractile amplitude. The data suggest that the native P2X(4) receptor is involved in mediating the P2 agonist-stimulated response in the heart. In characterizing the biochemical property of the P2X(4) receptor, antibody against cP2X(4)R detected a 44-kDa and a 58-kDa protein in the immunoblot. Inhibition of N-linked glycosylation by tunicamycin converted the 58-kDa protein to the 44-kDa protein, suggesting that the 58-kDa protein was a glycosylated P2X(4) receptor. The nonglycosylated 44-kDa P2X(4) receptor was resistant to various detergent/aqueous extraction, consistent with a role of glycosylation in maintaining its detergent solubility and hydrophilicity. Cross-linking the cell surface proteins with N-hydroxysuccinimide-SS-biotin followed by affinity precipitation with streptavidin-conjugated agarose and subsequent immunoblotting with anti-cP2X(4)R showed that only the glycosylated 58-kDa P2X(4) receptor was expressed on the cell surface, indicating an important role of glycosylation for the receptor's localization on the plasma membrane. These data revealed a novel physiologic function of the P2X(4) receptor and suggested the importance of N-linked glycosylation in its cell surface expression and detergent solubility.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15752-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
P2X4 receptor is a glycosylated cardiac receptor mediating a positive inotropic response to ATP.
pubmed:affiliation
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't