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  P2X(4) receptor is a glycosylated cardiac receptor mediating a positive inotropic response to ATP

Hu, B., Senkler, C., Yang, A., Soto, F., & Liang, B. T. (2002). P2X(4) receptor is a glycosylated cardiac receptor mediating a positive inotropic response to ATP. The Journal of Biological Chemistry, 277(18), 15752-15757.

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Hu, B., Author
Senkler, C., Author
Yang, A., Author
Soto, Florentina1, Author           
Liang, B. T., Author
Affiliations:
1Molecular biology of neuronal signals, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173656              

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 Abstract: 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 P2X(4) 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 Ca-45 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.

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Language(s): eng - English
 Dates: 2002-05-03
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 17447
ISI: 000175510400072
 Degree: -

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Title: The Journal of Biological Chemistry
  Other : JBC
Source Genre: Journal
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Publ. Info: Baltimore, etc. : American Society for Biochemistry and Molecular Biology [etc.]
Pages: - Volume / Issue: 277 (18) Sequence Number: - Start / End Page: 15752 - 15757 Identifier: ISSN: 0021-9258
CoNE: https://pure.mpg.de/cone/journals/resource/954925410826_1