title: GABA expression in the mammalian taste bud functions as a route of inhibitory cell-to-cell communication.
abstract: Recent advances have underscored cell-to-cell communication as an important component of the operation of taste buds with individual taste receptor cells (TRCs) communicating with one another by means of a number of neurotransmitters and neuropeptides, although functional roles are not yet understood. Here, we characterize the presence, distribution pattern, phenotype, and functional consequences of a previously undescribed inhibitory route within the taste bud mediated by the classic neurotransmitter GABA and its receptors. By using immunocytochemistry, subsets of TRCs within rat taste buds were identified as expressing GABA, and its synthetic enzyme glutamate decarboxylase (GAD). GAD expression was verified with Western blotting. Immunofluorescent studies revealed complex coexpression patterns of GAD with the TRC protein markers gustducin, neural cell adhesion molecule, protein gene product 9.5, and synaptosomal-associated protein of 25 kDa that collectively outline hardwired signaling pathways of GABAergic TRCs. RT-PCR and immunocytochemistry demonstrated that both GABA(A) and GABA(B) receptors are expressed in the taste bud. The later was observed in a subset TRCs paracrine to GAD-expressing TRCs. Physiological effects of GABA were examined by patch clamp recordings. GABA and the GABA(A) agonists muscimol and isoguvacine enhanced isolated chloride currents in a dose-dependent manner. Also, GABA and the GABA(B) agonist baclofen both elicited increases of the inwardly rectifying potassium currents that could be blocked by the GABA(B) receptor antagonist CGP 35348 and the G protein blocker GDP-betaS. Collectively, these data suggest that GABAergic TRCs are able to shape the final chemosensory output of the bud by means of processes of cell-to-cell modulation.
authors.affiliation: College of Dentistry, Ohio State University, 305 West 12th Street, Columbus, OH 43210, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Fang-li
authors.initials: FL
authors.lastname: Zhao
authors.forename: Tamara
authors.initials: T
authors.lastname: Kolli
authors.forename: Randy
authors.initials: R
authors.lastname: Hivley
authors.forename: Scott
authors.initials: S
authors.lastname: Herness
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D018118:Chloride Channels / Q000378:metabolism; D058785:GABA-A Receptor Agonists; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013650:Taste Buds / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018118:Chloride Channels; D058785:GABA-A Receptor Agonists; D015221:Potassium Channels; D021122:Protein Subunits; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase