Antagonism of metabotropic glutamate receptor 4 receptors by (RS)-α-cyclopropyl-4-phosphonophenylglycine alters the taste of amino acids in rats

Eschle, Benjamin K.; Eddy, Meghan C.; Delay, Eugene R.

doi:10.1016/j.neuroscience.2009.07.035

Cited by 13 publications

(15 citation statements)

References 49 publications

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“…Both mGluR1 and mGluR4 may function as umami taste receptors in taste bud cells independent of T1R1 or T1R3. Previous studies reported that CPPG inhibited responses to glutamate and l ‐AP4 in isolated rat taste cells (100 μ m , Lin & Kinnamon, 1999), as well as behavioural responses to these compounds in rats (1 m m , Eschle et al 2009) and mice (1 m m , Nakashima et al 2001). We found that M2‐type fibres transmit the CPPG‐sensitive components of glutamate responses in mice.…”

Section: Discussionmentioning

confidence: 92%

“…These agonists and antagonists were dissolved in distilled water with KOH to adjust their pH to 7.0. As previous studies have demonstrated that taste mGluRs have lower affinities than the corresponding brain‐type receptors (Chaudhari et al 2000; San Gabriel et al 2005) and behavioural taste responses to glutamate were inhibited by high concentrations of CPPG (1 m m ; Nakashima et al 2001; Eschle et al 2009), we used high concentrations of agonists and antagonists. To test potential effects of K + from KOH in these solutions, KCl at the same final concentration as the added KOH was added to the array of stimulus solutions.…”

Section: Methodsmentioning

confidence: 99%

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Umami taste in mice uses multiple receptors and transduction pathways

Yasumatsu

Ogiwara

Takai

et al. 2012

The Journal of Physiology

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Non-technical summary The distinctive umami taste elicited by L-glutamate and some other amino acids is thought to be initiated by G-protein-coupled receptors, such as heteromers of taste receptor type 1, members 1 and 3, and metabotropic glutamate receptors 1 and 4. We demonstrate the existence of multiple types of glutamate-sensitive gustatory nerve fibres and the contribution of multiple receptors and transduction pathways to umami taste. Such multiple systems for umami taste may differentially contribute to the behavioural preference for glutamate and discriminability of glutamate taste. AbstractThe distinctive umami taste elicited by L-glutamate and some other amino acids is thought to be initiated by G-protein-coupled receptors. Proposed umami receptors include heteromers of taste receptor type 1, members 1 and 3 (T1R1+T1R3), and metabotropic glutamate receptors 1 and 4 (mGluR1 and mGluR4). Multiple lines of evidence support the involvement of T1R1+T1R3 in umami responses of mice. Although several studies suggest the involvement of receptors other than T1R1+T1R3 in umami, the identity of those receptors remains unclear. Here, we examined taste responsiveness of umami-sensitive chorda tympani nerve fibres from wild-type mice and mice genetically lacking T1R3 or its downstream transduction molecule, the ion channel TRPM5. Our results indicate that single umami-sensitive fibres in wild-type mice fall into two major groups: sucrose-best (S-type) and monopotassium glutamate (MPG)-best (M-type). Each fibre type has two subtypes; one shows synergism between MPG and inosine monophosphate (S1, M1) and the other shows no synergism (S2, M2). In both T1R3 and TRPM5 null mice, S1-type fibres were absent, whereas S2-, M1-and M2-types remained. Lingual application of mGluR antagonists selectively suppressed MPG responses of M1-and M2-type fibres. These data suggest the existence of multiple receptors and transduction pathways for umami responses in mice. Information initiated from T1R3-containing receptors may be mediated by a transduction pathway including TRPM5 and conveyed by sweet-best fibres, whereas umami information from mGluRs may be mediated by TRPM5-independent pathway(s) and conveyed by glutamate-best fibres. Ami, amiloride; CPPG, (RS)-α-cyclopropyl-4-phosphonophenylglycine; CT, chorda tympani; ENaC, epithelial sodium channel; GAD67, glutamate decarboxylase 67; GL, glossopharyngeal; GMP, guanosine monophosphate; HEK, human embryonic kidney; IMP, inosine monophosphate; IP 3 R3, inositol 1,4,5-trisphosphate receptor 3; KO, knockout; L-Ala, L-alanine; L-AP4, L-(+)-2-amino-4-phosphonobutyrate; L-Arg, L-arginine hydrochloride; L-Cys, L-cysteine; L-Lys, L-lysine hydrochloride; mGluR1(mGluR4), metabotropic glutamate receptor type 1 (type 4); MPG, monopotassium glutamate; MSG, monosodium glutamate; NMDA, N -methyl-D-aspartic acid; QHCl, quinine hydrochloride; Quis, quisqualic acid; Suc, sucrose; TRPM5, transient receptor potential cation channel subfamily M member 5; WT, wild-type.

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Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Umami taste in mice uses multiple receptors and transduction pathways

Yasumatsu

Ogiwara

Takai

et al. 2012

The Journal of Physiology

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“…In addition, 0.1–3 m m ( RS )‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA) with and without 300 m m MSG, 0.1–3 m m ( RS )‐α‐cyclopropyl‐4‐phosphonophenylglycine (CPPG) with and without 300 m m MSG, the mixtures of 0.1–3 m m AIDA and CPPG with and without 300 m m MSG were used. These concentrations of antagonists were reported to affect taste responses to glutamate (Nakashima et al 2001; Eschle et al 2009; Yasumatsu et al 2012). For the CTA experiment, the CS was 300 m m MSG.…”

Section: Methodsmentioning

confidence: 99%

Taste responses in mice lacking taste receptor subunit T1R1

Kusuhara

Yoshida²,

Ohkuri³

et al. 2013

The Journal of Physiology

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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.

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“…In support of a role for mGlu4 in taste, the group III mGlu receptor antagonist CPPG decreased the amount of aversion for MSG and other amino acids when MSG served as the conditioned stimulus in a taste aversion test (Eschle et al, 2009). However, when CPPG was mixed with these amino acids, the strength of the learned taste aversions and cross-generalization were either decreased or increased, indicating that the antagonist was not only able to reduce the intensity of the stimulus experience but also changed the qualities of the sensory experience (Eschle et al, 2009). These authors propose that multiple receptors are involved in amino acid taste and that taste mGlu4 receptors contribute to the taste of MSG and at least some other L-amino acids.…”

Section: A the Initiation Sequelae Of A Mealmentioning

confidence: 97%

“…It is noteworthy that these truncated forms of mGlu receptors, also known as taste mGlu1 and taste mGlu4, lack a great portion of the glutamate-binding domain, (Chaudhari et al, 2009); consequently, the effective concentration of L-glutamate required to activate the taste mGlu receptor variants is higher than that needed for the full-length receptors (Chaudhari et al, 2000(Chaudhari et al, , 2009. In support of a role for mGlu4 in taste, the group III mGlu receptor antagonist CPPG decreased the amount of aversion for MSG and other amino acids when MSG served as the conditioned stimulus in a taste aversion test (Eschle et al, 2009). However, when CPPG was mixed with these amino acids, the strength of the learned taste aversions and cross-generalization were either decreased or increased, indicating that the antagonist was not only able to reduce the intensity of the stimulus experience but also changed the qualities of the sensory experience (Eschle et al, 2009).…”

Section: A the Initiation Sequelae Of A Mealmentioning

confidence: 99%