DIFFERENTIAL COUPLING OF G-ALPHA-Q FAMILY OF G-PROTEIN TO MUSCARINIC M-1 RECEPTOR AND NEUROKININ-2 RECEPTOR

The ligand binding signals to a wide variety of seven transmembrane ce ll surface receptors are transduced into intracellular signals through heterotrimeric G-proteins. Recently, there have been reports which sh ow diverse coupling patterns of ligand-activated receptors to the memb ers of Gq family alpha subunits. in order to shed some light on these complex signal processing networks, interactions between G alpha q fam ily of G protein and neurokinin-2 receptor as well as muscarinic M-1, 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 stimu lated with Various concentrations of carbachol and neurokinin A and th e agonist-dependent release of [H-3]inositol phosphates through phosph olipase C beta-1 activation was measured. Differential coupling of G a lpha q family of C-protein to muscarinic M-1, receptor and neurokinin- 2 receptor was observed. The neurokinin-2 receptor shows a ligand-medi ated response in membranes co-transfected with G alpha q, G alpha 11 a nd G alpha 14 but not G alpha 16 and the ability of the muscarinic M-1 receptor to activate phospholipase C through G alpha q/11 but not G a lpha 14 and G alpha 16 was demonstrated. Clearly G alpha q/11 can coup le M1 and neurokinin-2 receptor to activate phospholipase C. But, ther e are differences in the relative coupling of the Ga14 and Ga16 subuni ts to these receptors.