The cDNA encoding a novel P receptor was isolated from rat aortic smooth muscle cell library and functionally characterized. The cloned P receptor exhibits structural features characteristic of the G protein-coupled receptor family and shows 44 and 38% amino acid identity with previously cloned rat P and chicken P receptors, respectively. The cloned P receptor is functionally coupled to phospholipase C but not to adenylate cyclase in C6 rat glioma cells transfected with the cloned P expression vector. The rank order of agonist potency as judged by intracellular Ca mobilization responses is UTP > ADP = 2-methylthioATP > ADPS > ATP = ATPS, which is not compatible with any of the previously characterized P receptor subtypes. The nonselective P antagonists, suramin and reactive blue-2, inhibit nucleotide-induced phospholipase C activation in cells expressing the cloned P receptor. The cloned P 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 P receptor has pharmacological characteristics distinct from any of P receptor subtypes thus far identified and suggest the existence of a novel regulatory system by extracellular nucleotides of potential significance.

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