Journal of Biological Chemistry
Volume 270, Issue 44, 3 November 1995, Pages 26152-26158
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Cell Biology and Metabolism
Molecular Cloning and Functional Analysis of a Novel P2 Nucleotide Receptor (∗)

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The cDNA encoding a novel P2 receptor was isolated from rat aortic smooth muscle cell library and functionally characterized. The cloned P2 receptor exhibits structural features characteristic of the G protein-coupled receptor family and shows 44 and 38% amino acid identity with previously cloned rat P2U and chicken P2Y receptors, respectively. The cloned P2 receptor is functionally coupled to phospholipase C but not to adenylate cyclase in C6 rat glioma cells transfected with the cloned P2 expression vector. The rank order of agonist potency as judged by intracellular Ca2+ mobilization responses is UTP > ADP = 2-methylthioATP > ADPβS > ATP = ATPγS, which is not compatible with any of the previously characterized P2 receptor subtypes. The nonselective P2 antagonists, suramin and reactive blue-2, inhibit nucleotide-induced phospholipase C activation in cells expressing the cloned P2 receptor. The cloned P2 receptor mRNA is abundantly expressed in various rat tissues including lung, stomach, intestine, spleen, mesentery, heart, and, most prominently, aorta. The results indicate that the novel metabotropic P2 receptor has pharmacological characteristics distinct from any of P2 receptor subtypes thus far identified and suggest the existence of a novel regulatory system by extracellular nucleotides of potential significance.

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This work was supported by grants from the Ministry of Education, Science, and Culture of Japan and the Tsumura Foundation for Cardiovascular Research and by funds from the Japan Heart Foundation and the Japan Research Foundation for Clinical Pharmacology. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(TM)/EMBL Data Bank with accession number(s) D63665.