Abstract
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 α subunits. In order to shed some light on these complex signal processing networks, interactions between Gαq family of G protein and neurokinin-2 receptor as well as muscarinic M1 receptor, which are considered to be new thearpeutic targets in asthma, were studied. Using washed membranes from Cos-7 cells co-transfected with different Gαq 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 Gαq 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 Gαq, Gα11 and Gα14 but not Gα16 and the ability of the muscarinic M1 receptor to activate phospholipase C through Gαq/11 but not Gα14 and Gα16 was demonstrated. Clearly Gαq/11 can couple M1 and neurokinin-2 receptor to activate phospholipase C. But, there are differences in the relative coupling of the Gα14 and Gα16 subunits to these receptors.
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References Cited
Amatruda, T. T. III, Steele, D., Slepak, V. and Simon, M. I., Gα16, a G protein α subunitspecifically expressed in hematopoietic cells.Proc. Natl. Acad. Sci. USA 88, 5587–5591 (1991).
Barnes, P. J., Muscarinic receptors in airways: recent developments.J. Appl. Physiol., 68, 1777–1785 (1990a).
Barnes, P. J., Muscarinic receptor subtypes: implication for therapy.Agents Actions, 43(suppl.), 243–252 (1993b).
Berridge, M. J., Inositol trisphosphate and calcium signaling.Nature, 361, 315–325 (1993).
Berstein, G., Blank, J. L., Smrcka, A. V., Higashijma, T., Sternweis, P. C., Exton, J. H. and Ross, E. M., Reconstitution of agonist-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis using purified M1 receptor, Gq/11 and phospholipase C beta1.J. Biol. Chem., 267, 8081–8088 (1992).
Brauner-Osborne, H and Brann, M. Pharmacology of muscarinic acetylcholine receptor subtypes (m1-m5); high throughput assays in mammalian cells.Eur. J. Pharmacol., 295, 93–102 (1996).
Day, N. S., Berti-Mattera, L. N. and Eichberg, J., Muscarinic cholinergic receptor mediated phosphoinositide metabolism in peripheral nerve.J. Neurochem., 56, 1905–1913 (1991).
Ford, A. P., Eglen, R. M. and Whiting, R. L., Analysis of muscarinic cholinergic receptors mediating phosphoinositide hydrolysis in guinea pig cardiac muscle.Eur. J. Pharmacol., 225, 105–112 (1992).
Gilman, A. G., G protein: transducers of receptor-generated signals.Annu. Rev. Biochem., 56, 615–649 (1987).
Gudermann, T., Kalkbrenner, F. and Schulz, G., Diversity and selectivity of receptor-G protein interaction.Annu. Rev. Pharmacol. Toxicol., 36, 429–459 (1996).
Hellstrom, P. M., Murthy, K. S., Grider, J. R. and Makhlouf, G. M., Coexistence of three tachykinin receptors coupled to Ca2+ signaling pathways in intestinal muscle cells.J. Pharm. Exp. Ther., 270, 236–243 (1994).
Hulme, E. C., Birdsall, N. J. M. and Buckley, N. J., Muscarinic receptor subtypes.Annu. Rev. Pharmacol. Toxicol., 30, 633–673 (1990).
Hunter, J. C., Goedert, M. and Pinnock, R. D., Mammalian tachykinin-induced hydrolysis of inositol phospholipids in rat brain slices.Biochem. Biophys. Res. Commun., 127, 616–622 (1985).
Kwatra, M. M., Schwinn, D. A., Schreurs, J., Blank, J. L., Kim, C. M., Benovic, J. L., Krause, J. E., Caron, M. G., Lefkowitz, R. J., The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2.J. Biol. Chem., 268, 9161–9164 (1993).
Longmore, J., Swain, C. J. and Hill, R. G., Neurokinin receptors.DN&P., 8, 5–23 (1995).
Laniyonu, A., Sliwinski, Lis. E. and Fleming, N., Different tachykinin receptor subtypes are coupled to the phosphoinositide or cAMP signal transduction pathway in rat submandibular cells.FEBS Lett., 240, 186–190 (1988).
Lee, C., Park, D., Wu, D., Rhee, S. G. and Simon, M. I., Members of the Gqα subunit gene family activate phospholipase C β isozymes.J. Biol. Chem., 267, 16044–16047 (1992).
Maclagan, J. and Barnes, P. J., Muscarinic pharmacology of the airways.Trends in Pharmacol. Sci., Dec. suppl. 88–92 (1989).
Nakajima, Y., Tsuchida, K., Negishi, M., Ito, S. and Nakanish, S., Direct linkage of three tachykinin receptors to stimulation of both phosphotidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese hamster ovary cells.J. Biol. Chem., 267, 2437–2442 (1992).
Naline, E., Devillier, P., Drapeau, G., Toty, L., Bakolach, H., Regoli, D. and Advenier, C., Characterization of nerokinin effects and receptor selectivity in human isolated bronchi.Am. Rev. Resp. Dis., 140, 679–686 (1989).
Offermanns, S. and Simon, M., Gα15 and Gα16 couple a wide variety of receptors to phospholipase C.J. Biol. Chem., 270, 15175–15180 (1995).
Rhee, S. and Bae, Y., Regulation of phosphoinositide-specific phospholipase C isozymes.J. Biol. Chem., 272, 15045–15048 (1997).
Ross, E. M. and Berstein, G., Regulation of the M1 muscarinic receptor-Gq-phospholipase C-beta pathway by nucleotide exchange and GTP hydrolysis.Life Sci., 52, 413–419 (1993).
Simon, M. I., Strathmann, M. P. and Gautam, N., Diversity of G proteins in signal transduction.Science, 252, 802–808 (1991).
Wilkie, T., Scherle, P., Strathmann, M., Slepak, V. and Simon, M.I., Characterization of G-protein a subunits in the Gq class: Expression in murine tissues and in stromal and hematopoietic cell lines.Proc. Natl. Acad. Sci. USA, 88, 10049–10053 (1991).
Wu, D., Katz, A., Lee, C. H. and Simon, M. I., Activation of phospholipase C by α1-adrenergic receptors is mediated by the a subunits of Gq family.J. Biol. Chem., 267, 25798–25802 (1992b).
Wu, D., Lee, C. H., Rhee, S. G. and Simon, M. I., Activation of phospholipase C by the a subunits of the Gq and G11 proteins in transfected cos-7 cells.J. Biol. Chem., 267, 1811–1817 (1992a).
Yamashita, K., Koide, M. and Aiyoshi, Y., Effects of substance P on thyroidal cyclic AMP levels and thyroid hormone release from canine.Life Sci., 32, 2163–2166 (1983).
Zaagsma, J., Roffel, A. F. and Meurs, H., Muscarinic control of airway function.Life. Sci., 60, 1061–1068 (1997).
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Lee, C.H., Shin, I.C., Kang, J.S. et al. Differential coupling of Gαq family of G-protein to muscarinic M1 receptor and neurokinin-2 receptor. Arch. Pharm. Res. 21, 423–428 (1998). https://doi.org/10.1007/BF02974637
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DOI: https://doi.org/10.1007/BF02974637