Molecular Mechanisms for Sweet-suppressing Effect of Gymnemic Acids

Sanematsu, Keisuke; Kusakabe, Yuko; Shigemura, Noriatsu; Hirokawa, Takatsugu; Nakamura, Seiji; Imoto, Toshiaki; Ninomiya, Yuzo

doi:10.1074/jbc.m114.560409

Cited by 59 publications

(62 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, we confirmed that these receptors were functional, except for a heterodimer mTas1r2 + hTAS1R3 as described previously ( Supplementary Fig. S1 ) 11 . These receptors showed responses to artificial sweeteners SC45647 and saccharin.…”

Section: Resultssupporting

confidence: 82%

See 1 more Smart Citation

Intracellular acidification is required for full activation of the sweet taste receptor by miraculin

Sanematsu

Kitagawa

Yoshida

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice. The sweet taste induced by MCL is more intense when acidification occurs with weak acids as opposed to strong acids. MCL interacts with the human sweet receptor subunit hTAS1R2, but the mechanisms by which the acidification of MCL activates the sweet taste receptor remain largely unexplored. The work reported here speaks directly to this activation by utilizing a sweet receptor TAS1R2 + TAS1R3 assay. In accordance with previous data, MCL-applied cells displayed a pH dependence with citric acid (weak acid) being right shifted to that with hydrochloric acid (strong acid). When histidine residues in both the intracellular and extracellular region of hTAS1R2 were exchanged for alanine, taste-modifying effect of MCL was reduced or abolished. Stronger intracellular acidification of HEK293 cells was induced by citric acid than by HCl and taste-modifying effect of MCL was proportional to intracellular pH regardless of types of acids. These results suggest that intracellular acidity is required for full activation of the sweet taste receptor by MCL.

show abstract

Section: Resultssupporting

confidence: 82%

“…Human TAS1Rs and Gαl6-gust44 expression constructs were generated in the pEF-DEST51 Gateway vector (Life Technologies Corporation) 11 25 . Mouse Tas1r2 and Tas1r3 were cloned as described 26 27 .…”

Section: Methodsmentioning

confidence: 99%

Intracellular acidification is required for full activation of the sweet taste receptor by miraculin

Sanematsu

Kitagawa

Yoshida

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…The sweet taste receptor antagonists lactisole (27, 28) and gymnemic acid (67, 68) blocked glucose-mediated inhibition of SCC calcium responses (Fig. 4A).…”

Section: Resultsmentioning

confidence: 88%

Bacterial d -amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells

et al. 2017

View full text Add to dashboard Cite

In the upper respiratory epithelium, bitter and sweet taste receptors present in solitary chemosensory cells influence antimicrobial innate immune defense responses. Whereas activation of the bitter taste receptor (T2R) stimulates surrounding epithelial cells to release antimicrobial peptides, activation of the sweet taste receptor (T1R) in the same cells inhibits this response. It is thought that this mechanism exists to control the magnitude of antimicrobial peptide release based upon the sugar content of airway surface liquid. We hypothesized that D-amino acids, which are produced by various bacteria and activate T1R in taste receptor cells in the mouth, may also activate T1R in the airway. Here, we show that both the T1R2 and T1R3 subunits of the sweet taste receptor (T1R2/3) are present in the same chemosensory cells of primary human sinonasal epithelial cultures. Respiratory isolates of Staphylococcus species, but not Pseudomonas aeruginosa, produced at least two D-amino acids that activate the sweet taste receptor. In addition to inhibiting P. aeruginosa biofilm formation, D-amino acids derived from Staphylococcus inhibited T2R-mediated signaling and defensin secretion in sinonasal cells by activating T1R2/3. D-amino acid–mediated activation of T1R2/3 also enhanced epithelial cell death during challenge with Staphylococcus aureus in the presence of the bitter-receptor–activating compound denatonium benzoate. These data establish a potential mechanism for interkingdom signaling in the airway mediated by bacterial D-amino acids and the mammalian sweet taste receptor in airway chemosensory cells.

show abstract

“…The affinity and geometry of inclusion of aescin in the cavity of β-CD, having an inner diameter of 0.78 nm, is not known. Furthermore, and in spite of the many reports pointing to the preference of triterpenic guests for the larger host γ-CD [ 15 – 16 18 , 20 ], with cavity diameter of 0.95 nm, the γ-CD·aescin inclusion complex, herein reported, had not been studied to date. The present work demonstrates the stronger affinity of aescin to γ-CD and the formation of a 1:1 inclusion complex, presenting its most plausible geometry.…”

Section: Introductionmentioning

confidence: 85%

“…The ability of γ-CD to interact with triterpenic glycosides is known for over two decades, being first reported as a sequestering agent and sweetness inhibitor for strognin, a natural sweetener found in the Malaysian plant Staurogyne merguensi [ 15 ]. With glycemnic acid, a sweetness suppressing agent, γ-CD also acts as inhibitor, thus restoring one’s ability to taste sweets [ 16 ]. Inclusion of triterpenic compounds of medicinal interest is a topic of growing interest due to the ability of cyclodextrins to increase the solubility of these molecules.…”

Section: Introductionmentioning

confidence: 99%

Association of aescin with β- and γ-cyclodextrins studied by DFT calculations and spectroscopic methods

Ramos¹,

Vaz

Braga

et al. 2017

Beilstein J. Nanotechnol.

View full text Add to dashboard Cite

Background: Aescin, a natural mixture of saponins occurring in Aesculus hippocastanum, exhibits important flebotonic properties, being used in the treatment of chronic venous insufficiency in legs. The inclusion of aescin into cyclodextrins (CDs) is a technical solution for its incorporation into the textile of stockings, but details of the physicochemistry of these host-guest systems are lacking. This work investigates the inclusion of aescin into the cavities of two native cyclodextrins, β-CD and γ-CD.

show abstract

Molecular Mechanisms for Sweet-suppressing Effect of Gymnemic Acids

Cited by 59 publications

References 51 publications

Intracellular acidification is required for full activation of the sweet taste receptor by miraculin

Intracellular acidification is required for full activation of the sweet taste receptor by miraculin

Bacterial d -amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells

Association of aescin with β- and γ-cyclodextrins studied by DFT calculations and spectroscopic methods

Contact Info

Product

Resources

About