Abscisic acid acts as a blocker of the bitter taste G protein-coupled receptor T2R4

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DOIResolve DOI: http://doi.org/10.1021/acs.biochem.5b00265
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TypeArticle
Journal titleBiochemistry
ISSN0006-2960
Volume54
Issue16
Pages26222631; # of pages: 10
AbstractBitter taste receptors (T2Rs) belong to the G protein-coupled receptor superfamily. In humans, 25 T2Rs mediate bitter taste sensation. In addition to the oral cavity, T2Rs are expressed in many extraoral tissues, including the central nervous system, respiratory system, and reproductive system. To understand the mechanistic roles of the T2Rs in oral and extraoral tissues, novel blockers or antagonists are urgently needed. Recently, we elucidated the binding pocket of T2R4 for its agonist quinine, and an antagonist and inhibitory neurotransmitter, γ-aminobutyric acid. This structure−function information about T2R4 led us to screen the plant hormone abscisic acid (ABA), its precursor (xanthoxin), and catabolite phaseic acid for their ability to bind and activate or inhibit T2R4. Molecular docking studies followed by functional assays involving calcium imaging confirmed that ABA is an antagonist with an IC50 value of 34.4 ± 1.1 μM. However, ABA precursor xanthoxin acts as an agonist on T2R4. Interestingly, molecular model-guided site-directed mutagenesis suggests that the T2R4 residues involved in quinine binding are also predominantly involved in binding to the novel antagonist, ABA. The antagonist ability of ABA was tested using another T2R4 agonist, yohimbine. Our results suggest that ABA does not inhibit yohimbineinduced T2R4 activity. The discovery of natural bitter blockers has immense nutraceutical and physiological significance and will help in dissecting the T2R molecular pathways in various tissues.
Publication date
LanguageEnglish
AffiliationAquatic and Crop Resource Development; National Research Council Canada
Peer reviewedYes
NRC number56147
NPARC number21275419
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Record identifier2382b173-5ed8-4b2a-ad7d-57ad49d585a4
Record created2015-07-13
Record modified2016-05-09
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