title: Pungent products from garlic activate the sensory ion channel TRPA1.
abstract: Garlic belongs to the Allium family of plants that produce organosulfur compounds, such as allicin and diallyl disulfide (DADS), which account for their pungency and spicy aroma. Many health benefits have been ascribed to Allium extracts, including hypotensive and vasorelaxant activities. However, the molecular mechanisms underlying these effects remain unknown. Intriguingly, allicin and DADS share structural similarities with allyl isothiocyanate, the pungent ingredient in wasabi and other mustard plants that induces pain and inflammation by activating TRPA1, an excitatory ion channel on primary sensory neurons of the pain pathway. Here we show that allicin and DADS excite an allyl isothiocyanate-sensitive subpopulation of sensory neurons and induce vasodilation by activating capsaicin-sensitive perivascular sensory nerve endings. Moreover, allicin and DADS activate the cloned TRPA1 channel when expressed in heterologous systems. These and other results suggest that garlic excites sensory neurons primarily through activation of TRPA1. Thus different plant genera, including Allium and Brassica, have developed evolutionary convergent strategies that target TRPA1 channels on sensory nerve endings to achieve chemical deterrence.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, CA 94143, USA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Bautista
authors.forename: Pouya
authors.initials: P
authors.lastname: Movahed
authors.forename: Andrew
authors.initials: A
authors.lastname: Hinman
authors.forename: Helena E
authors.initials: HE
authors.lastname: Axelsson
authors.forename: Olov
authors.initials: O
authors.lastname: Sterner
authors.forename: Edward D
authors.initials: ED
authors.lastname: Högestätt
authors.forename: David
authors.initials: D
authors.lastname: Julius
authors.forename: Sven-Eric
authors.initials: SE
authors.lastname: Jordt
authors.forename: Peter M
authors.initials: PM
authors.lastname: Zygmunt
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D004220:Disulfides / Q000737:chemistry / Q000494:pharmacology*; D005737:Garlic / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology; D013441:Sulfinic Acids / Q000737:chemistry / Q000494:pharmacology*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000498:Allyl Compounds; D015220:Calcium Channels; D004220:Disulfides; D009419:Nerve Tissue Proteins; D010936:Plant Extracts; D013441:Sulfinic Acids; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C006452:allicin; C028009:diallyl disulfide; D015740:Calcitonin Gene-Related Peptide