Differential coupling of G alpha q family of G-protein to muscarinic M1 receptor and neurokinin-2 receptor.
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 alpha subunits. In order to shed some light on these complex signal processing networks, interactions between G alpha q family of G protein and neurokinin-2 receptor as well as muscarinic M1 receptor, which are considered to be new therapeutic 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 [3H]inositol phosphates through phospholipase C beta-1 activation was measured. Differential coupling of G alpha q family of G-protein to muscarinic M1 receptor and neurokinin-2 receptor was observed. The neurokinin-2 receptor shows a ligand-mediated response in membranes co-transfected with G alpha q, G alpha 11 and G alpha 14 but not G alpha 16 and the ability of the muscarinic M1 receptor to activate phospholipase C through G alpha q/11 but not G alpha 14 and G alpha 16 was demonstrated. Clearly G alpha q/11 can couple M1 and neurokinin-2 receptor to activate phospholipase C. But, there are differences in the relative coupling of the G alpha 14 and G alpha 16 subunits to these receptors.
Lee
C H
CH
Department of Pharmacology, Hanyang University, College of Medicine, Seoul, Korea.
Shin
I C
IC
Kang
J S
JS
Koh
H C
HC
Ha
J H
JH
Min
C K
CK
D000818:Animals; D019556:COS Cells; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D054799:Phospholipase C beta; D011485:Protein Binding; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D007527:Isoenzymes; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D018041:Receptors, Neurokinin-2; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002217:Carbachol; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins