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Tytuł pozycji:

The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR.

Tytuł:
The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR.
Autorzy:
Huang J; Department of Environmental Health and Engineering, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205; .
Lam H; Department of Environmental Health and Engineering, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205.
Koziol-White C; Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, NJ 08854.; Rutgers Institute for Translational Medicine and Science, New Brunswick, NJ 08901.
Limjunyawong N; Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Kim D; Center for Personalized Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.
Kim N; Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, NJ 08854.
Karmacharya N; Rutgers Institute for Translational Medicine and Science, New Brunswick, NJ 08901.
Rajkumar P; Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Firer D; Department of Environmental Health and Engineering, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205.
Dalesio NM; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Jude J; Rutgers Institute for Translational Medicine and Science, New Brunswick, NJ 08901.
Kurten RC; Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205.
Pluznick JL; Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Deshpande DA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Translational Medicine, Jane and Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, PA 19107.
Penn RB; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Translational Medicine, Jane and Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, PA 19107.
Liggett SB; Center for Personalized Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.; Department of Medical Engineering, University of South Florida, Tampa, FL 33612.
Panettieri RA Jr; Rutgers Institute for Translational Medicine and Science, New Brunswick, NJ 08901.
Dong X; Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.; Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
An SS; Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, NJ 08854; .; Rutgers Institute for Translational Medicine and Science, New Brunswick, NJ 08901.
Źródło:
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Nov 10; Vol. 117 (45), pp. 28485-28495. Date of Electronic Publication: 2020 Oct 23.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: Washington, DC : National Academy of Sciences
MeSH Terms:
Anoctamin-1/*metabolism
Cystic Fibrosis Transmembrane Conductance Regulator/*metabolism
Muscle, Smooth/*metabolism
Neoplasm Proteins/*metabolism
Receptors, Odorant/*metabolism
Adenylyl Cyclases/metabolism ; Bronchi/metabolism ; Calcium/metabolism ; Cells, Cultured ; Humans ; Lung/metabolism ; Muscle Contraction/physiology ; Muscle Relaxation ; Myocytes, Smooth Muscle/metabolism ; Receptors, Odorant/genetics
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Grant Information:
R01 HL058506 United States HL NHLBI NIH HHS; R01 AI135186 United States AI NIAID NIH HHS; P01 HL114471 United States HL NHLBI NIH HHS; R01 HL045967 United States HL NHLBI NIH HHS; R01 NS054791 United States NS NINDS NIH HHS; United States HHMI Howard Hughes Medical Institute; R01 HL137030 United States HL NHLBI NIH HHS
Contributed Indexing:
Keywords: G proteins; airway smooth muscle; asthma; olfactory receptor; single-cell analysis
Substance Nomenclature:
0 (ANO1 protein, human)
0 (Anoctamin-1)
0 (CFTR protein, human)
0 (Neoplasm Proteins)
0 (OR2W3 protein, human)
0 (Receptors, Odorant)
126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
EC 4.6.1.1 (Adenylyl Cyclases)
SY7Q814VUP (Calcium)
Entry Date(s):
Date Created: 20201024 Date Completed: 20210104 Latest Revision: 20211102
Update Code:
20240105
PubMed Central ID:
PMC7668088
DOI:
10.1073/pnas.2003111117
PMID:
33097666
Czasopismo naukowe
The recent discovery of sensory (tastant and odorant) G protein-coupled receptors on the smooth muscle of human bronchi suggests unappreciated therapeutic targets in the management of obstructive lung diseases. Here we have characterized the effects of a wide range of volatile odorants on the contractile state of airway smooth muscle (ASM) and uncovered a complex mechanism of odorant-evoked signaling properties that regulate excitation-contraction (E-C) coupling in human ASM cells. Initial studies established multiple odorous molecules capable of increasing intracellular calcium ([Ca 2+ ] i ) in ASM cells, some of which were (paradoxically) associated with ASM relaxation. Subsequent studies showed a terpenoid molecule (nerol)-stimulated OR2W3 caused increases in [Ca 2+ ] i and relaxation of ASM cells. Of note, OR2W3-evoked [Ca 2+ ] i mobilization and ASM relaxation required Ca 2+ flux through the store-operated calcium entry (SOCE) pathway and accompanied plasma membrane depolarization. This chemosensory odorant receptor response was not mediated by adenylyl cyclase (AC)/cyclic nucleotide-gated (CNG) channels or by protein kinase A (PKA) activity. Instead, ASM olfactory responses to the monoterpene nerol were predominated by the activity of Ca 2+ -activated chloride channels (TMEM16A), including the cystic fibrosis transmembrane conductance regulator (CFTR) expressed on endo(sarco)plasmic reticulum. These findings demonstrate compartmentalization of Ca 2+ signals dictates the odorant receptor OR2W3-induced ASM relaxation and identify a previously unrecognized E-C coupling mechanism that could be exploited in the development of therapeutics to treat obstructive lung diseases.
Competing Interests: The authors declare no competing interest.
(Copyright © 2020 the Author(s). Published by PNAS.)

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