| A molecularly identified P2Y receptor simultaneously activates phospholipase C and inhibits adenylyl cyclase and is nonselectively activated by all nucleoside triphosphates. | |
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MedLine Citation:
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PMID: 10727529 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We recently cloned and expressed a novel P2Y receptor (tp2y receptor) from a turkey cDNA library. Expression of this receptor in 1321N1 human astrocytoma cells confers nucleotide-dependent stimulation of phospholipase C activity; however, as we demonstrate here, it also confers nucleotide-dependent inhibition of adenylyl cyclase. Both the phospholipase C and adenylyl cyclase responses were promoted by receptor agonists over a similar range of concentrations. Moreover, not only did UTP and ATP activate the avian receptor but ITP, GTP, xanthosine 5'-triphosphate, and CTP were also agonists, with EC(50) values ranging between 0.1 and 1 microM. Similar potencies, rank-order, and selectivity of nucleotide agonists were also demonstrated for intracellular Ca(2+) mobilization measured during a 30-s stimulation under constant superfusion conditions. This observation indicates that receptor activation by nucleoside 5'-triphosphates is not produced by interconversion of these nucleotides into ATP or UTP. Pretreatment of cells with pertussis toxin completely abolished the inhibitory effect of nucleotide agonists on adenylyl cyclase, whereas the activation of phospholipase C was only partially inhibited. These results demonstrate that the avian P2Y receptor is a nucleoside triphosphate receptor of broad agonist selectivity that interacts with both pertussis toxin-insensitive and -sensitive G proteins to activate phospholipase C and to inhibit adenylyl cyclase. This is the first cloned P2Y receptor that is clearly Gi/adenylyl cyclase-linked. |
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Authors:
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J L Boyer; S M Delaney; D Villanueva; T K Harden |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular pharmacology Volume: 57 ISSN: 0026-895X ISO Abbreviation: Mol. Pharmacol. Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-05-04 Completed Date: 2000-05-04 Revised Date: 2010-01-14 |
Medline Journal Info:
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Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 805-10 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, The School of Medicine, University of North Carolina, Chapel Hill, North Carolina 7599-7365, USA. boyerl@med.unc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Adenylate Cyclase / antagonists & inhibitors, metabolism* Animals Cloning, Molecular Cytidine Triphosphate / metabolism Enzyme Activation Enzyme Inhibitors GTP-Binding Proteins / metabolism Guanosine Triphosphate / metabolism Humans Nucleotides / metabolism* Receptors, Purinergic P2 / genetics, metabolism* Tumor Cells, Cultured Turkeys Type C Phospholipases / metabolism* Uridine Triphosphate / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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GM38213/GM/NIGMS NIH HHS; HL54889/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Nucleotides; 0/Receptors, Purinergic P2; 0/purinergic receptor P2Y2; 56-65-5/Adenosine Triphosphate; 63-39-8/Uridine Triphosphate; 65-47-4/Cytidine Triphosphate; 86-01-1/Guanosine Triphosphate; EC 3.1.4.-/Type C Phospholipases; EC 3.6.1.-/GTP-Binding Proteins; EC 4.6.1.1/Adenylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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