title: Effect of the umami peptides on the ligand binding and function of rat mGlu4a receptor might implicate this receptor in the monosodium glutamate taste transduction.
abstract: 1. The effect of several metabotropic ligands and di- or tripeptides were tested on the binding of [3H]-L(+)-2-amino-4-phosphonobutyric acid ([3H]-L-AP4) on rat mGlu4 receptor. For selected compounds, the functional activity was determined on this receptor using the guanosine-5'[gamma-35S]-thiotriphosphate [gamma-35S]-GTP binding assay. 2. Using the scintillation proximity assay, [3H]-L-AP4 saturation analysis gave binding parameters K(D) and Bmax values of 150 nM and 9.3 pmoles mg-1 protein, respectively. The specific binding was inhibited concentration-dependently by several mGlu receptor ligands, and their rank order of affinity was established. 3. Several peptides inhibited the [3H]-L-AP4 binding with the following rank order of potency: glutamate-glutamate>glutamate-glutamate-leucine=aspartate - glutamate>>glutamate - glutamate-aspartate>lactoyl-glutamate>>aspartate-aspartate. Aspartate-phenylalanine-methyl ester (aspartame) was inactive up to 1 mM and guanosine-5'-monophosphate and inosine-5'-monophosphate were inactive up to 100 micronM. 4. The [gamma-35S]-GTP binding functional assay was used to determine the agonist activities of the different compounds. For the rat mGlu4 agonists, L-AP4 and L-glutamate, the correlation between their occupancy and activation of the receptor was close to one. The peptides, Glu-Glu, Asp-Glu and Glu-Glu-Asp failed to stimulate the [gamma-35S]-GTP binding at receptor occupancy greater than 80% and Glu-Glu-Leu appeared to be a weak partial agonist. These peptides did not elicit a clear dose-dependent umami perception. However, Glu-lac showed a good correlation between its potency to stimulate the [gamma-35S]-GTP binding and its affinity for displacement of [3H]-L-AP4 binding. These data are in agreement with the peptide taste assessment in human subjects, which showed that the acid derivatives of glutamate had characteristics similar to umami.
authors.affiliation: Pharma Division Preclinical CNS Research Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Monastyrskaia
authors.forename: K
authors.initials: K
authors.lastname: Lundstrom
authors.forename: D
authors.initials: D
authors.lastname: Plahl
authors.forename: G
authors.initials: G
authors.lastname: Acuna
authors.forename: C
authors.initials: C
authors.lastname: Schweitzer
authors.forename: P
authors.initials: P
authors.lastname: Malherbe
authors.forename: V
authors.initials: V
authors.lastname: Mutel
mesh_terms: D000328:Adult; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D005421:Flavoring Agents / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology*; D011422:Propionates / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012970:Sodium Glutamate / Q000494:pharmacology*; D013649:Taste / Q000187:drug effects*
chemical_list: C114785:2-amino-4-phosphono-propinate; D005421:Flavoring Agents; D008024:Ligands; D009842:Oligopeptides; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; C093917:delicious peptide; D012970:Sodium Glutamate; C108823:metabotropic glutamate receptor 4