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Purification and Reconstitution of TRPV1 for Spectroscopic Analysis
Published on: July 3, 2018
A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic
Héctor Salazar1, Itzel Llorente, Andrés Jara-Oseguera
1Departamento de Biofísica, Instituto de Fisiología Celular, Circuito Exterior S/N, Ciudad Universitaria, Universidad Nacional Autónoma de México, México, D.F., 04510, Mexico.
Abstract:
Some members of the transient receptor potential (TRP) family of cation channels mediate sensory responses to irritant substances. Although it is well known that TRPA1 channels are activated by pungent compounds found in garlic, onion, mustard and cinnamon extracts, activation of TRPV1 by these extracts remains controversial. Here we establish that TRPV1 is activated by pungent extracts from onion and garlic, as well as by allicin, the active compound in these preparations, and participates together with TRPA1 in the pain-related behavior induced by this compound. We found that in TRPV1 these agents act by covalent modification of cysteine residues. In contrast to TRPA1 channels, modification of a single cysteine located in the N-terminal region of TRPV1 was necessary and sufficient for all the effects we observed. Our findings point to a conserved mechanism of activation in TRP channels, which provides new insights into the molecular basis of noxious stimuli detection.
Insights
Transient receptor potential vanilloid 1 (TRPV1) channels are activated by pungent compounds like allicin from garlic and onions. This activation, involving cysteine modification, contributes to pain perception alongside TRPA1 channels.
Area of Science:
- Molecular biology
- Neuroscience
- Sensory science
Background:
- Transient receptor potential (TRP) channels are crucial for sensory perception.
- TRPA1 channels are known activators of pungent compounds, but TRPV1 activation is debated.
Purpose of the Study:
- To investigate the activation of TRPV1 channels by pungent compounds found in garlic and onion.
- To elucidate the molecular mechanism of TRPV1 activation by these compounds and its role in pain.
Main Methods:
- Utilized pungent extracts from onion and garlic, and the compound allicin.
- Investigated channel activation through covalent modification of cysteine residues.
- Examined pain-related behaviors in the context of TRP channel activity.
Main Results:
- Established that TRPV1 channels are activated by onion and garlic extracts and allicin.
- Demonstrated that allicin activates TRPV1 through covalent modification of a single N-terminal cysteine residue.
- Showed that TRPV1, along with TRPA1, participates in pain behaviors induced by allicin.
Conclusions:
- TRPV1 activation by pungent compounds occurs via covalent cysteine modification, similar to TRPA1.
- A single cysteine modification in TRPV1 is sufficient for activation by these agents.
- Findings reveal a conserved activation mechanism in TRP channels, advancing understanding of noxious stimuli detection.
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