Presentation Details
| Identification of the Bitter Taste Receptors for Tuberculosis and Anti-Infection Medications Rachel Lin, Lauren Caronia, Peihua Jiang. Monell Chemical Senses Center, Philadelphia, PA, USA |
Abstract
Bitterness is a complex human taste sensation, mediated by 25 functional bitter taste receptor genes (TAS2R) that collectively detect thousands of structurally diverse bitter compounds (Meyehof et al., 2010). These G-protein-coupled receptors, expressed on taste cells, initiate afferent signaling to the brain in response to bitter stimuli (Bachmanov and Beauchamp, 2007). Few effective strategies exist to block the bitterness of essential medications, contributing to poor adherence in vulnerable populations. Prior work identified a subset of the 25 TAS2Rs as mediators of the bitterness of antiviral, antischistosomal, and antimalarial active pharmaceutical ingredients (APIs). Tenofovir alafenamide (TAF), an HIV treatment, activates TAS2R1, TAS2R8, TAS2R14, and TAS2R39 (Schwiebert et al., 2021; Caronia et al., 2023). However, the TAS2Rs underlying the bitterness of tuberculosis (TB) drugs remain largely uncharacterized. We hypothesize that TB drugs and other essential APIs elicit bitterness through a similar set of TAS2Rs. To test this, 17 APIs used for TB and other infectious diseases were screened for activation of all 25 TAS2Rs using cell-based functional assays. HEK293 cells were transiently transfected with individual TAS2Rs and the chimeric G protein Gα16-gust44 to couple receptor activation to calcium mobilization. For 8 APIs, solubility issues, endogenous activity, or lack of bitterness at tested concentrations prevented assessment of TAS2R activation. The remaining 9 APIs activated a subset of TAS2Rs, most frequently TAS2R1, TAS2R8, TAS2R14, and TAS2R39; TAS2R10 and TAS2R46 also responded to some compounds. These findings suggest a small receptor subset drives bitterness across a variety of TB and anti-infection medications, informing strategies to improve drug palatability and compliance.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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