Bitter tastants relax the mouse gallbladder smooth muscle independent of signaling through tuft cells and bitter taste receptors.

Animals Gallbladder / metabolism Receptors, G-Protein-Coupled / metabolism Mice Muscle, Smooth / metabolism TRPM Cation Channels / metabolism Muscle Relaxation / drug effects Dextromethorphan / pharmacology Signal Transduction Quinine / pharmacology Taste / physiology Myocytes, Smooth Muscle / metabolism Quaternary Ammonium Compounds / pharmacology Noscapine / pharmacology Male Mice, Knockout Calcium / metabolism Mice, Inbred C57BL Tuft Cells
Cholecystokinin Denatonium Dextromethorphan Quinine Taste transduction cascade Transient receptor potential family member 5

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
08 Aug 2024
Historique:
received: 29 02 2024
accepted: 02 08 2024
medline: 9 8 2024
pubmed: 9 8 2024
entrez: 8 8 2024
Statut: epublish

Résumé

Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder. In organ bath experiments, the bitter tastants denatonium, quinine, dextromethorphan, and noscapine, dose-dependently relaxed the pre-contracted gallbladder. Utilizing gene-deficient mouse strains, neither transient receptor potential family member 5 (TRPM5), nor the Tas2r143/Tas2r135/Tas2r126 gene cluster, nor tuft cells proved to be required for this relaxation, indicating direct action upon smooth muscle cells (SMC). Accordingly, denatonium, quinine and dextromethorphan increased intracellular calcium concentration preferentially in isolated gallbladder SMC and, again, this effect was independent of TRPM5. RT-PCR revealed transcripts of Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, and analysis of gallbladders from mice lacking tuft cells revealed preferential expression of Tas2r108 and Tas2r137 in tuft cells. A TAS2R143-mCherry reporter mouse labeled tuft cells in the gallbladder epithelium. An in silico analysis of a scRNA sequencing data set revealed Tas2r expression in only few cells of different identity, and from in situ hybridization histochemistry, which did not label distinct cells. Our findings demonstrate profound tuft cell- and TRPM5-independent relaxing effects of bitter tastants on gallbladder smooth muscle, but do not support the concept that these effects are mediated by bitter receptors.

Identifiants

DOI: 10.1038/s41598-024-69287-6 PMID: 39117690
pubmed: 39117690
doi: 10.1038/s41598-024-69287-6
pii: 10.1038/s41598-024-69287-6
doi:

Substances chimiques

Receptors, G-Protein-Coupled 0
TRPM Cation Channels 0
Dextromethorphan 7355X3ROTS
Quinine A7V27PHC7A
denatonium 4IK22DF4OU
taste receptors, type 2 0
Quaternary Ammonium Compounds 0
Noscapine 8V32U4AOQU
Trpm5 protein, mouse 0
Calcium SY7Q814VUP

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

18447

Subventions

Organisme : Wolfgang Kummer
ID : KU688/8-1
Organisme : Burkhard Schütz
ID : SCHU1259/10-1

Informations de copyright

© 2024. The Author(s).

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Auteurs

Maryam Keshavarz (M)

Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, Giessen, Germany. maryam.keshavarz@med.uni-augsburg.de.
Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University, Giessen, Germany. maryam.keshavarz@med.uni-augsburg.de.
Anatomy and Cell Biology, Institute of Theoretical Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany. maryam.keshavarz@med.uni-augsburg.de.

Anna-Lena Ruppert (AL)

Institute for Anatomy and Cell Biology, Philipps-University, Marburg, Germany.

Mirjam Meiners (M)

Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, Giessen, Germany.
Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University, Giessen, Germany.

Krupali Poharkar (K)

Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, Giessen, Germany.
Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University, Giessen, Germany.

Shuya Liu (S)

III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

Wafaa Mahmoud (W)

Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, Giessen, Germany.
Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University, Giessen, Germany.
Department of Anatomy, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.

Sarah Winterberg (S)

Institute for Anatomy and Cell Biology, Philipps-University, Marburg, Germany.

Petra Hartmann (P)

Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, Giessen, Germany.
Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University, Giessen, Germany.

Petra Mermer (P)

Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, Giessen, Germany.
Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University, Giessen, Germany.

Alexander Perniss (A)

Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, Giessen, Germany.
Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University, Giessen, Germany.
Division of Allergy and Clinical Immunology, Department of Medicine, Jeff and Penny Vinik Center for Allergic Disease Research, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Stefan Offermanns (S)

Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University, Giessen, Germany.
Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

Wolfgang Kummer (W)

Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, Giessen, Germany. wolfgang.kummer@anatomie.med.uni-giessen.de.
Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University, Giessen, Germany. wolfgang.kummer@anatomie.med.uni-giessen.de.

Burkhard Schütz (B)

Institute for Anatomy and Cell Biology, Philipps-University, Marburg, Germany. schuetzb@staff.uni-marburg.de.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Système digestif › Voies biliaires › Vésicule biliaire › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Tissus › Muscles › Muscles lisses › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Canaux cationiques TRP › Canaux cationiques TRPM › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Contraction musculaire › Relâchement musculaire › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Composés polycycliques › Hydrocarbures aromatiques polycycliques › Phénanthrènes › Morphinanes › Dextrométhorphane › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinoléines › Quinine › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Sensation › Goût › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes du muscle lisse › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Composés chimiques organiques › Composés onium › Composés d'ammonium quaternaire › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Isoquinoléines › Noscapine › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Calcium › Bitter tastants relax the mouse gallbladder...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Bitter tastants relax the mouse gallbladder...