title: The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.
abstract: Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response.
authors.affiliation: Department of Otolaryngology, and Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, Colorado 80045, and eric.larson@ucdenver.edu.
authors.forename: Eric D
authors.identifier: http://orcid.org/0000-0002-2881-4861
authors.initials: ED
authors.lastname: Larson
authors.affiliation: Department of Otolaryngology, and Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, Colorado 80045, and.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Vandenbeuch
authors.affiliation: Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, 14588 Nuthetal, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Voigt
authors.affiliation: Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, 14588 Nuthetal, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyerhof
authors.affiliation: Department of Otolaryngology, and Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, Colorado 80045, and.
authors.forename: Sue C
authors.initials: SC
authors.lastname: Kinnamon
authors.affiliation: Department of Cell and Developmental Biology, Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, Colorado 80045, and.
authors.forename: Thomas E
authors.identifier: http://orcid.org/0000-0001-5923-5099
authors.initials: TE
authors.lastname: Finger
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000818:Animals; D005260:Female; D005830:Geniculate Ganglion / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010424:Pentobarbital / Q000494:pharmacology; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013266:Stilbamidines / Q000378:metabolism; D013649:Taste / Q000235:genetics / Q000502:physiology; D013650:Taste Buds / Q000187:drug effects / Q000502:physiology*; D015293:Transducin / Q000378:metabolism
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000759:Adjuvants, Anesthesia; D058477:Receptors, Purinergic P2X3; D044406:Receptors, Serotonin, 5-HT3; D013266:Stilbamidines; D049452:Green Fluorescent Proteins; C075192:gustducin; D012701:Serotonin; D000255:Adenosine Triphosphate; D015293:Transducin; D010424:Pentobarbital
keywords: 5ht3; barbiturate; calcium; geniculate ganglion; serotonin; taste signaling