Taste responses in mice lacking taste receptor subunit T1R1

Abstract

Key points• The taste receptor heterodimer T1R1 + T1R3, metabotropic glutamate receptors (mGluRs) and/or their variants may function as umami taste receptors.• Here, we used newly developed T1R1 −/− mice and examined the role of T1R1 and mGluRs in taste detection.• The T1R1−/− mice exhibited seriously diminished synergistic responses to glutamate and inosine monophosphate but not to glutamate alone and significantly smaller responses to sweeteners.• Addition of mGluR antagonists significantly inhibited responses to glutamate in both T1R1 −/− and heterozygous T1R1 +/− mice.• Taken together, these results suggest that T1R1 mainly contributes to umami taste synergism and partly to sweet sensitivity, while mGluRs are involved in the detection of umami compounds. AbstractThe T1R1 receptor subunit acts as an umami taste receptor in combination with its partner, T1R3. In addition, metabotropic glutamate receptors (brain and taste variants of mGluR1 and mGluR4) are thought to function as umami taste receptors. To elucidate the function of T1R1 and the contribution of mGluRs to umami taste detection in vivo, we used newly developed knock-out (T1R1 −/− ) mice, which lack the entire coding region of the Tas1r1 gene and express mCherry in T1R1-expressing cells. Gustatory nerve recordings demonstrated that T1R1 −/− mice exhibited a serious deficit in inosine monophosphate-elicited synergy but substantial residual responses to glutamate alone in both chorda tympani and glossopharyngeal nerves. Interestingly, chorda tympani nerve responses to sweeteners were smaller in T1R1 Conditioned taste aversion tests demonstrated that both T1R1−/− and T1R1 +/− mice were equally capable of discriminating glutamate from other basic taste stimuli. Avoidance conditioned to glutamate was significantly reduced by addition of mGluR antagonists. These results suggest that T1R1-expressing cells mainly contribute to umami taste synergism and partly to sweet sensitivity and that mGluRs are involved in the detection of umami compounds. CPPG, (RS)-α-cyclopropyl-4-phosphonophenylglycine; CS, conditioned stimulus; CT, chorda tympani; CTA, conditioned taste aversion; DW, distilled water; GAD67, glutamate decarboxylase 67; GL, glossopharyngeal; GLAST, glutamate/aspartate transporter; IMP, inosine monophosphate; KO, knock-out; L-AP4, L(+)-2-amino-4-phosphonobutyrate; mGluR, metabotropic glutamate receptor; MPG, monopotassium glutamate; MSG, monosodium glutamate; PLCβ2, phospholipase C β2; QHCl, quinine hydrocholoride; QSO 4 , quinine sulfate; SNAP25, synaptosomal-associated protein 25; T1R1 (T1R2 or T1R3), taste receptor family 1 member 1 (2 or 3); TRPM5, transient receptor potential cation channel subfamily M member 5; US, unconditioned stimulus; WT, wild-type.

Taste buds: cells, signals and synapses

“…However, studies using an independently generated Tas1r3 -knockout line (see above) showed that the behavioural and neural responses of these mice to umami compounds (MSG and IMP) were nearly normal 22, 40 . Furthermore, a second line of mice in which Tas1r1 was knocked out also demonstrated near-normal responses to umami compounds in taste bud cells and nerves; the only major change was that the nucleotide-mediated augmentation of umami taste was lost 41 . Thus, it seems that T1R1–T1R3 responds primarily to mixtures of MSG and nucleotides.…”

“…Most type II cells express one class of taste GPCR — namely, taste receptor type 1 (T1R) or T2R — and correspondingly respond only to one taste quality (for example, sweet or bitter, but not both) 131, 132 . It should be noted that T1R1, T1R2 and T1R3 are often co-expressed in taste bud cells, and, accordingly, responses to both sweet and umami stimuli can be detected in the same cells 41, 114 . The type II cells in a taste bud can differ in their expression of taste GPCRs such that each taste bud can respond to multiple taste stimuli.…”

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

“…In this study we used the paradigmatic umami ligand MSG to activate T1R1/T1R3 receptors. Since MSG may also activate other amino acid-sensing receptors, we also employed the 5=-ribonucleotide IMP, an allosteric activator specific for T1R1 (27,49). Thus the combination of MSG and IMP shows that the effects are specific to T1R1/T1R3 activation.…”

“…Moreover, inosine 5=-monophosphate (IMP) is a potentiator of T1R1/T1R3 activation but is not a potentiator at other putative umami receptors (CaSR, metabotropic glutamate receptor, or G protein-coupled receptor family C, group 6, member A) (12,27,33,49). Therefore, IMP can be used to pharmacologically determine if T1R1/T1R3 receptors are involved in changes in GI motility, as has been done in the characterization of umami taste.…”

Taste perception, associated hormonal modulation, and nutrient intake

“…18,26 Although some evidence exists to the contrary, 27 it has been generally accepted that individual type II receptor cells only express receptors for a specific taste quality -sweet, umami, or bitter (i.e., these three classes of taste stimuli are detected by nonoverlapping populations of taste cells within the taste bud). Sweet tastants, including artificial sweeteners, bind to a heterodimer of the G protein-coupled receptors, T1R2 and T1R3.…”