Publication

Role and mechanism of transient receptor potential (TRP) channels in gustatory and chemesthetic sensations associated with dietary molecules

Céline Riera
2008
Thèse EPFL
Résumé

"Chemosensory perception", the perception of food chemicals, relies on the complex cooperation of gustatory, olfactory and somatosensory detection systems. In the oral cavity, the taste buds and the lingual branch of the trigeminal nerve are the organs that respond to ingested dietary molecules. Remarkable advances in the understanding of the physiology of these systems have been achieved by identification of key proteins directly implicated in the detection machinery. Among them, several members of the Transient Receptor Potential (TRP) superfamily of ion channels play critical roles in sensory physiology, with contribution in taste, touch, thermosensation and nociception (perception of harmful stimuli). However, even though important key players have been identified, much less is known about their exact role and the specific tuning of their response. In the framework of this Ph.D thesis, I focussed on several dietary molecules possessing complex perceptions and studied their sensory targets. To achieve this, in vitro and in vivo approaches were combined. In a first step, the goal was to answer a simple question: is metallic taste a unique sensation, as are sweet or bitter modalities? To address this issue, the sensory pathways of prototypical metallic tastants being divalent salts of metal cations and artificial sweeteners were evaluated. It was aimed at determining if these molecules could stimulate both somatosensory neurons projecting in the oral cavity and taste buds contained in the papillae. The screening for receptor candidates contained in sensory neurons revealed that these molecules were stimulating TRPV1, the capsaicin (from red hot chilli peppers) receptor. Calcium transients were observed in dissociated sensory neurons from the Dorsal Root Ganglia (DRG) expressing TRPV1 and by using calcium and voltage imaging techniques, a selective stimulation when heterologously expressed in HEK 293 cells was also showed. To elucidate the pathways involved in the perception of sweeteners and metal cations, taste preference assays were performed using mice lacking TRPV1 and TRPM5, the latter being a key channel involved in downstream signalling of sweet, umami and bitter tastes. The results revealed that preference profiles were modified when these two channels were lacking. Direct stimulation of TRPM5 with metallic stimuli did not result in channel opening consistent with a downstream role of this channel in taste cells after activation of the taste GPCR. Remarkably, it was observed that wild type mice displayed strong preference for two metallic stimuli, FeSO4 and ZnSO4 and this preference was absent in mice lacking TRPM5. It was further showed that suppression of T1R3, the receptor of sweet and umami stimuli in taste cells also leads to indifference in the mice, suggesting that these metals induce pleasantness possibly through one of these pathways. Collectively, these data showed that artificial sweeteners and divalent salts elicit biphasic responses in mice, with an hedonic phase involving T1R3-TRPM5 pathways and an aversive phase recruiting TRPM5 and TRPV1 pathways. In addition, it was aimed at obtaining a better understanding of trigeminal sensory targets stimulated by culinary spices and their activation mechanisms. For this purpose, two spices remarkable for their pungent and tingling attributes were selected: Sichuan pepper and Afromomum Melegueta. The results indicate that the active molecules contained in these spices stimulate DRG neurons and activate TRPV1 and TRPA1, the capsaicin and the cinnamaldehyde (from cinnamon) receptors, respectively. Their stimulation of TRPA1 requires covalent binding at specific intracellular cysteine residues in the N-termini whereas no such interactions were occurring with TRPV1. The results present novel insight into the co-stimulation of TRPA1 and TRPV1 where the two channels, even though sensitive to the same compounds, react via different modes. In addition, by conducting taste preference assays in the TRPV1 KO mice, it was shown that the aversive response is mainly accounted by TRPV1 with a residual aversion that possibly underlies a TRPA1 response. In summary, these results show that several TRP channels are key elements to detect dietary molecules such as artificial sweeteners, divalent salts and pungent spices. This is achieved by different processes including receptor modulation by the chemical, covalent binding at the receptor and indirect stimulation in the case of store-operated channel such as TRPM5.

À propos de ce résultat
Cette page est générée automatiquement et peut contenir des informations qui ne sont pas correctes, complètes, à jour ou pertinentes par rapport à votre recherche. Il en va de même pour toutes les autres pages de ce site. Veillez à vérifier les informations auprès des sources officielles de l'EPFL.
Concepts associés (55)
Goût
Le goût (également écrit gout dans la nouvelle orthographe), ou la gustation, est le sens qui permet d'identifier les substances chimiques sous forme de solutions par l'intermédiaire de chémorécepteurs situés sur la langue (récepteurs de Vugo). Il joue un rôle important dans l'alimentation en permettant d'analyser la saveur des aliments. Par métonymie, on appelle aussi « goût » chacune des saveurs distinguées par le sens du goût (ce que l'odeur est à l'odorat).
Transient receptor potential channel
Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), TRPV ("V" for vanilloid), TRPVL ("VL" for vanilloid-like), TRPM ("M" for melastatin), TRPS ("S" for soromelastatin), TRPN ("N" for no mechanoreceptor potential C), and TRPA ("A" for ankyrin). Group 2 consists of TRPP ("P" for polycystic) and TRPML ("ML" for mucolipin).
Système sensoriel
Un système sensoriel est une partie du système nerveux responsable de la sensation. Il regroupe les récepteurs sensoriels, les voies nerveuses, et les parties du cerveau responsables du traitement de l'information sensorielle. L'ensemble des systèmes sensoriels se divisent en sensibilité générale ou somesthésie et en sens dits spécifiques : la vision, l'odorat, le goût, l'ouïe et le toucher. Il existe sept sens : les cinq sens vu ci-dessus (vision, odorat, goût, ouïe et toucher), ainsi que le système vestibulaire et le système proprioceptif.
Afficher plus
Publications associées (37)

Striatal Dopamine Signals and Reward Learning

Carl Petersen, Sylvain Crochet, Yanqi Liu, Parviz Ghaderi, Mauro Pulin, Anthony Pierre Robert Renard, Christos Sourmpis, Pol Bech Vilaseca, Meriam Malekzadeh, Robin François Virginien Dard

We are constantly bombarded by sensory information and constantly making decisions on how to act. In order to optimally adapt behavior, we must judge which sequences of sensory inputs and actions lead to successful outcomes in specific circumstances. Neuro ...
Oxford2023

Hydraulically Amplified Electrostatic Taxels (HAXELs) for Full Body Haptics

Herbert Shea, Edouard Franck Vincent Gustave Leroy

The ability to mechanically stimulate touch receptors over the entire body is a key feature for fully immersive and highly realistic virtual reality experience. Haptic stickers, flexible arrays of HAXELs (hydraulically amplified TAXels), that enable cutane ...
WILEY2023

Anatomical and functional characterization of neocortical circuits involved in transforming whisker sensory processing into goal-directed licking

Georgios Foustoukos

The choice of an action upon perception of an external stimulus, arriving at a sensory organ of an animal, depends on previous experiences and outcomes throughout its life. In the rodent brain, the underlying mechanisms involved in simple sensorimotor tran ...
EPFL2021
Afficher plus
MOOCs associés (20)
Simulation Neurocience
Learn how to digitally reconstruct a single neuron to better study the biological mechanisms of brain function, behaviour and disease.
Simulation Neurocience
Learn how to digitally reconstruct a single neuron to better study the biological mechanisms of brain function, behaviour and disease.
Simulation Neurocience
Learn how to digitally reconstruct a single neuron to better study the biological mechanisms of brain function, behaviour and disease.
Afficher plus

Graph Chatbot

Chattez avec Graph Search

Posez n’importe quelle question sur les cours, conférences, exercices, recherches, actualités, etc. de l’EPFL ou essayez les exemples de questions ci-dessous.

AVERTISSEMENT : Le chatbot Graph n'est pas programmé pour fournir des réponses explicites ou catégoriques à vos questions. Il transforme plutôt vos questions en demandes API qui sont distribuées aux différents services informatiques officiellement administrés par l'EPFL. Son but est uniquement de collecter et de recommander des références pertinentes à des contenus que vous pouvez explorer pour vous aider à répondre à vos questions.