title: Metabotropic glutamate receptors are involved in the detection of IMP and L-amino acids by mouse taste sensory cells.
abstract: G-protein-coupled receptors are thought to be involved in the detection of umami and L-amino acid taste. These include the heterodimer taste receptor type 1 member 1 (T1r1)+taste receptor type 1 member 3 (T1r3), taste and brain variants of mGluR4 and mGluR1, and calcium sensors. While several studies suggest T1r1+T1r3 is a broadly tuned lLamino acid receptor, little is known about the function of metabotropic glutamate receptors (mGluRs) in L-amino acid taste transduction. Calcium imaging of isolated taste sensory cells (TSCs) of T1r3-GFP and T1r3 knock-out (T1r3 KO) mice was performed using the ratiometric dye Fura 2 AM to investigate the role of different mGluRs in detecting various L-amino acids and inosine 5' monophosphate (IMP). Using agonists selective for various mGluRs such as (RS)-3,5-dihydroxyphenylglycine (DHPG) (an mGluR1 agonist) and L-(+)-2-amino-4-phosphonobutyric acid (l-AP4) (an mGluR4 agonist), we evaluated TSCs to determine if they might respond to these agonists, IMP, and three L-amino acids (monopotassium L-glutamate, L-serine and L-arginine). Additionally, we used selective antagonists against different mGluRs such as (RS)-L-aminoindan-1,5-dicarboxylic acid (AIDA) (an mGluR1 antagonist), and (RS)-α-methylserine-O-phosphate (MSOP) (an mGluR4 antagonist) to determine if they can block responses elicited by these L-amino acids and IMP. We found that L-amino acid- and IMP-responsive cells also responded to each agonist. Antagonists for mGluR4 and mGluR1 significantly blocked the responses elicited by IMP and each of the L-amino acids. Collectively, these data provide evidence for the involvement of taste and brain variants of mGluR1 and mGluR4 in L-amino acid and IMP taste responses in mice, and support the concept that multiple receptors contribute to IMP and L-amino acid taste.
authors.affiliation: Department of Biology and Vermont Chemosensory Group, Marsh Life Science, 109 Carrigan Drive, The University of Vermont, Burlington, VT 05405, United States. Electronic address: spalchou@uvm.edu.
authors.forename: S
authors.initials: S
authors.lastname: Pal Choudhuri
authors.affiliation: Department of Biology and Vermont Chemosensory Group, Marsh Life Science, 109 Carrigan Drive, The University of Vermont, Burlington, VT 05405, United States. Electronic address: rona.delay@uvm.edu.
authors.forename: R J
authors.initials: RJ
authors.lastname: Delay
authors.affiliation: Department of Biology and Vermont Chemosensory Group, Marsh Life Science, 109 Carrigan Drive, The University of Vermont, Burlington, VT 05405, United States. Electronic address: eugene.delay@uvm.edu.
authors.forename: E R
authors.initials: ER
authors.lastname: Delay
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007292:Inosine Nucleotides / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects*; D013650:Taste Buds / Q000166:cytology*; D055697:Taste Perception / Q000187:drug effects / Q000502:physiology*
chemical_list: D000596:Amino Acids; D018683:Excitatory Amino Acid Agents; D007292:Inosine Nucleotides; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; C431926:taste receptors, type 1; D049452:Green Fluorescent Proteins; D002118:Calcium
keywords: IMP; T1r3 knockout mice; l-amino acids; mGluR1; mGluR4; taste