title: Complex formation and functional interaction between adenosine A1 receptor and type-1 metabotropic glutamate receptor.
abstract: The adenosine A1 receptor (A1R) is a G protein-coupled receptor (GPCR) for adenosine, a ubiquitous neuromodulator, and thus regulates neuronal excitability, as well as arousal and sensitivity to pain. In addition, we have previously described a new mode of action for A1R: in cerebellar Purkinje cells, its activation attenuates neuronal responses to glutamate, as mediated by the type-1 metabotropic glutamate receptor (mGluR1). mGluR1 is also a GPCR, and elicits such responses as long-term depression of the postsynaptic response to glutamate, a cellular basis for cerebellar motor learning. Here, we explore in greater detail the interaction between A1R and mGluR1 using non-neuronal cells. Co-immunoprecipitation and Förster resonance energy transfer (FRET) analysis reveal that A1R and mGluR1 form a complex. Furthermore, we found that mGluR1 activation inhibits A1R signaling, as measured by changes in intracellular cAMP. These findings demonstrate that A1R and mGluR1 have the intrinsic ability to form a heteromeric complex and mutually modulate signaling. This interaction may represent a new form of intriguing GPCR-mediated cellular responses.
authors.affiliation: Department of Pharmacology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: ykamiku@juntendo.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kamikubo
authors.affiliation: Laboratory for Neural Information Technology, Graduate School of Science and Engineering, University of Toyama, 3190 Gokufu, Toyama, Toyama 930-8555, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Tabata
authors.affiliation: Department of Pharmacology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Hakushun
authors.initials: H
authors.lastname: Sakairi
authors.affiliation: Department of Pharmacology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Pharmacology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D031541:Fluorescence Resonance Energy Transfer; D005971:Glutamates; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D036881:Long-Term Synaptic Depression / Q000235:genetics; D020239:Receptor Cross-Talk / Q000502:physiology*; D043682:Receptor, Adenosine A1 / Q000378:metabolism* / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D005971:Glutamates; D043682:Receptor, Adenosine A1; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D000242:Cyclic AMP
keywords: Adenosine receptor; FRET; GPCR; Metabotropic glutamate receptor; cAMP