title: Muscarinic acetylcholine receptor M3 modulates odorant receptor activity via inhibition of β-arrestin-2 recruitment.
abstract: The olfactory system in rodents serves a critical function in social, reproductive and survival behaviours. Processing of chemosensory signals in the brain is dynamically regulated in part by an animal's physiological state. We previously reported that type 3 muscarinic acetylcholine receptors (M3-Rs) physically interact with odorant receptors (ORs) to promote odour-induced responses in a heterologous expression system. However, it is not known how M3-Rs affect the ability of olfactory sensory neurons (OSNs) to respond to odours. Here, we show that an M3-R antagonist attenuates odour-induced responses in OSNs from wild-type, but not M3-R-null, mice. Using a novel molecular assay, we demonstrate that the activation of M3-Rs inhibits the recruitment of β-arrestin-2 to ORs, resulting in a potentiation of odour-induced responses in OSNs. These results suggest a role for acetylcholine in modulating olfactory processing at the initial stages of signal transduction in the olfactory system.
authors: 1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA [2] University Program of Genetics and Genomics, Duke University, Duke, North Carolina 27710, USA.
authors: Yue
authors: Y
authors: Jiang
authors: 1] Medical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA [2] Cell and Molecular Biology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors: Yun Rose
authors: 0000000280774975
authors: YR
authors: Li
authors: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors: Huikai
authors: H
authors: Tian
authors: 1] Cell and Molecular Biology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA [2] Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors: Minghong
authors: M
authors: Ma
authors: 1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Neurobiology, Duke Institute for Brain Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors: Hiroaki
authors: H
authors: Matsunami
mesh_terms: D000818:Animals; D019390:Arrestins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology; D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009812:Odorants; D018034:Olfactory Receptor Neurons; D018408:Patch-Clamp Techniques; D011759:Pyrrolidines / Q000494:pharmacology; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018035:Receptors, Odorant / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605254:ARRB2 protein, human; C000605258:Arrb2 protein, mouse; D019390:Arrestins; D001572:Benzofurans; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D043587:Receptor, Muscarinic M3; D018035:Receptors, Odorant; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C101207:darifenacin; D000242:Cyclic AMP; D010738:Type C Phospholipases