Pungent Products from Garlic Activate the Sensory Ion Channel TRPA1

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-08, Vol.102 (34), p.12248-12252
• Main Authors: Bautista, Diana M, Movahed, Pouya, Hinman, Andrew, Axelsson, Helena E, Sterner, Olov, Högestätt, Edward D, Julius, David, Jordt, Sven-Eric, Zygmunt, Peter M
• Format: Article
• Language: English
• Subjects: Allium sativum; Allyl Compounds - chemistry; Allyl Compounds - pharmacology; Basic Medicine; Biological Sciences; Brassica; Calcitonin Gene-Related Peptide - metabolism; Calcium; Calcium Channels - metabolism; Cells, Cultured; Disulfides; Disulfides - chemistry; Disulfides - pharmacology; Farmakologi och toxikologi; Garlic; Garlic - metabolism; Humans; Immunohistochemistry; Ions; Isothiocyanates; Läkemedelskemi; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinal Chemistry; Medicinska och farmaceutiska grundvetenskaper; Mustards; Nerve Tissue Proteins - agonists; Nerve Tissue Proteins - metabolism; Neurons; Nociceptors - metabolism; Oocytes; Pharmacology and Toxicology; Plant Extracts - metabolism; Plant Extracts - pharmacology; Sensory neurons; Sensory perception; Smell; Sulfinic Acids - chemistry; Sulfinic Acids - pharmacology; Transient Receptor Potential Channels - agonists; Transient Receptor Potential Channels - metabolism; TRPA1 Cation Channel; TRPC cation channels; Vasodilation; Vasodilation - drug effects
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0505356102

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.