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TitleVagal nerve TRPV3 regulates sedative-mediated appeasement.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 123, Issue 16, Page e2525757123, Year 2026
Publish dateApr 21, 2026
AuthorsPeiyu Wang / Jinpiao Zhu / Xuteng Lu / Chang Chen / Bomin Gao / Wanjiang Tao / Keyu Xia / Yang Song / Qiong Shi / Hongcun Gai / Panhao Xiao / Feng Liu / Peiyuan Pang / Yang Li / Xiaoyi Mo / Xiao-Dong Wang / Chang Xie / Dongdong Li / Zongze Zhang / Jing Yao /
PubMed AbstractAromatic essential oils (EOs) exhibit anxiolytic properties, yet their neural and molecular mechanisms remain to be understood. Here, we found that citronellal, an EO derived from lemongrass, ...Aromatic essential oils (EOs) exhibit anxiolytic properties, yet their neural and molecular mechanisms remain to be understood. Here, we found that citronellal, an EO derived from lemongrass, alleviates stress-related anxiety by modulating vagal tone. We identified transient receptor potential vanilloid 3 (TRPV3) channel in nodose ganglion (NG) as the molecular target of citronellal. TRPV3 was also observed to mediate the antistress effects of the inhaled anesthetic sevoflurane. Both sedatives attenuated acute restraint stress-induced hyperactivity of heart and breath rates via glutamatergic neurotransmission along NG-to-caudal nucleus tractus solitarius (cNTS) pathway. This effect was abolished by surgical vagotomy, , or NG-specific knockdown. Cryo-EM structural analysis revealed that sevoflurane occupies a pore-proximal fenestration site, while citronellal binds to the vanilloid site. Re-expression of wild-type TRPV3, but not loss-of-function TRPV3 mutants TRPV3(A560L) or TRPV3(V662A), in NG neurons restored the mouse's response to both sedatives, thereby modulating heart and respiratory rates. Together, these findings establish peripheral TRPV3 as a multisensory ligand-gated node for vagal modulation of stress responses, and help instruct pathway-specific anxiolytics.
External linksProc Natl Acad Sci U S A / PubMed:41989856 / PubMed Central
MethodsEM (single particle)
Resolution3.29 Å
Structure data

64082

9ued

EMDB-64082, PDB-9ued:
Cryo-EM structure of human TRPV3 in complex with sevoflurane determined in MSP2N2 nanodisc
Method: EM (single particle) / Resolution: 3.29 Å

Chemicals

PDB-1ipi:
CRYSTAL STRUCTURE OF THE ARCHAEAL HOLLIDAY JUNCTION RESOLVASE HJC FROM PYROCOCCUS FURIOSUS FORM II

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Transient Receptor Potential Vanilloid 3

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