Abstract
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 > ADP beta S > ATP = ATP gamma S, 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.
Highlights
P2 nucleotide receptors mediate a wide variety of physiological responses to extracellular nucleotides, including vascular smooth muscle contraction and relaxation, neurotransmission, and endocrine and exocrine secretion [1, 2]
In the present report we demonstrate the isolation of a cDNA encoding a novel P2 receptor subtype from rat aortic smooth muscle cell cDNA library, which is coupled to the Ca2ϩ phospholipase C messenger system and shows a distinct agonist specificity from any other known P2 receptor
Cell Culture—Primary cultures of rat aortic smooth muscle (RASM)1 cells were obtained by the explant method [20]
Summary
P2 nucleotide receptors mediate a wide variety of physiological responses to extracellular nucleotides, including vascular smooth muscle contraction and relaxation, neurotransmission, and endocrine and exocrine secretion [1, 2]. In the present report we demonstrate the isolation of a cDNA encoding a novel P2 receptor subtype from rat aortic smooth muscle cell cDNA library, which is coupled to the Ca2ϩ phospholipase C messenger system and shows a distinct agonist specificity from any other known P2 receptor. This receptor is predominantly expressed in rat aorta and several other tissues
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