Multiple sweet receptors and transduction pathways revealed in knockout mice by temperature dependence and gurmarin sensitivity

Tadahiro Ohkuri, Keiko Nakano, Nao Horio, Masafumi Jyotaki, Robert F. Margolskee, Yuzo Ninomiya

    Research output: Contribution to journalArticle

    50 Citations (Scopus)

    Abstract

    Sweet taste transduction involves taste receptor type 1, member 2 (T1R2), taste receptor type 1, member 3 (T1R3), gustducin, and TRPM5. Because knockout (KO) mice lacking T1R3, gustducin's Gα subunit (Gαgust), or TRPM5 exhibited greatly reduced, but not abolished responses of the chorda tympani (CT) nerve to sweet compounds, it is likely that multiple sweet transduction pathways exist. That gurmarin (Gur), a sweet taste inhibitor, inhibits some but not all mouse CT responses to sweet compounds supports the existence of multiple sweet pathways. Here, we investigated Gur inhibition of CT responses to sweet compounds as a function of temperature in KO mice lacking T1R3, Gαgust, or TRPM5. In T1R3-KO mice, responses to sucrose and glucose were Gur sensitive (GS) and displayed a temperature-dependent increase (TDI). In Gαgust-KO mice, responses to sucrose and glucose were Gur-insensitive (GI) and showed a TDI. In TRPM5-KO mice, responses to glucose were GS and showed a TDI. All three KO mice exhibited no detectable responses to SC45647, and their responses to saccharin displayed neither GS nor a TDI. For all three KO mice, the lingual application of pronase, another sweet response inhibitor, almost fully abolished responses to sucrose and glucose but did not affect responses to saccharin. These results provide evidence for 1) the existence of multiple transduction pathways underlying responses to sugars: a T1R3-independent GS pathway for sucrose and glucose, and a TRPM5-independent temperature sensitive GS pathway for glucose; 2) the requirement for Gαgust in GS sweet taste responses; and 3) the existence of a sweet independent pathway for saccharin, in mouse taste cells on the anterior tongue.

    Original languageEnglish
    JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
    Volume296
    Issue number4
    DOIs
    Publication statusPublished - Apr 1 2009

    Fingerprint

    Knockout Mice
    Temperature
    Glucose
    Saccharin
    Sucrose
    Tongue
    Chorda Tympani Nerve
    Pronase
    Gymnema sylvestre Gurmarin protein
    Gur

    All Science Journal Classification (ASJC) codes

    • Physiology
    • Physiology (medical)

    Cite this

    Multiple sweet receptors and transduction pathways revealed in knockout mice by temperature dependence and gurmarin sensitivity. / Ohkuri, Tadahiro; Nakano, Keiko; Horio, Nao; Jyotaki, Masafumi; Margolskee, Robert F.; Ninomiya, Yuzo.

    In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 296, No. 4, 01.04.2009.

    Research output: Contribution to journalArticle

    Ohkuri, Tadahiro ; Nakano, Keiko ; Horio, Nao ; Jyotaki, Masafumi ; Margolskee, Robert F. ; Ninomiya, Yuzo. / Multiple sweet receptors and transduction pathways revealed in knockout mice by temperature dependence and gurmarin sensitivity. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2009 ; Vol. 296, No. 4.
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