KMID : 0043319980210040423
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Archives of Pharmacal Research 1998 Volume.21 No. 4 p.423 ~ p.428
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Differential Coupling of Gq Family of G-protein to Muscarinic Receptor and Neurokinin-2-Receptor
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Lee Chang-Ho
Shin In-Chul Kang Ju-Seop Koh Hyun-Chul Ha Ji-Hee Min Chul-Ki
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Abstract
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The ligand binding signals to a wide variety of seven transmembrane cell surface receptors are transduced into intracellular signals through heterotrimeric G-proteins. Recently, there have been reports which show diverse coupling patterns of ligand-activated receptors to the members of Gq family subunits. In order to shed some light on these complex signal processing networks, interactions between Gq family of G protein and neurokinin-2 receptor as well as muscarinic M receptor, which are considered to be new thearpeutic targets in asthma, were studied. Using washed membranes from Cos-7 cells co-transfected with different G.alpha.q and receptor cDNAs, the receptors were stimulated with various concentrations of carbachol and neurokinin A and the agonist-dependent release of []inositol phosphates through phospholipase C beta-1 activation was measured. Differential coupling of Gaq family of G-protein to muscarinic M receptor and neurokinin-2 receptor was observed. The neurokinin-2 receptor shows a ligand-mediated response in membranes co-transfected with Gq, G11 and G14 but not G16 and the ability of the muscarinic receptor to activate phospholipase C through G/11 but not G14 and G16 was demonstrated. Clearly G/11 can couple and neurokinin-2 receptor to activate phospholipase C. But, there are differences in the relative coupling of the G14 and G16 subunits to these receptors.
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KEYWORD
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Muscarinic receptor, Neurokinin-2 receptor, Gaq G-protein, Phospholipase C beta, Signal transduction, Phosphoinositide
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