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TRP channels as therapeutic targets in IBS 81 4 upregulation of TRPV1 was found. The question whether increased capsaicin responsiveness in IBS relates to individual TRPV1 sensitivity or TRPV1 expression thus remains without a decisive answer. Table 4.2 Identified agonists and physical stimuli of TRP channels discussed in this paper. 16,55,56,110-112 Channel Exogenous agonists Physical stimuli Endogenous agonists TRPV1 Capsaicin (red pepper), polygodial (mountain pepper), piperine (black pepper), gingerol (ginger), olvanil, resiniferatoxin, camphor, diphenylboronic anhydride, double- knot toxin (DkTx), vanillotoxin (tarantula toxin), phenylacetylrinvanil, 2-aminoethoxydiphenyl borate (2- APB), evodiamine, cannabidiol, cannabigerol (Thermal >42°C) Acid (pH < 6), lipoxygenase products ( e.g . 12-(S)-hydroperoxyeicosatetraenoic acid (12S-HPETE), 15-(S)- hydroperoxyeicosatetraenoic acid (15S- HPETE), leukotriene B4 (LTB4), 5-(S)- hydroxyeicosatetraenoic acid (5S-HETE)), reactive oxygen species (ROS), adenosine, ATP, lysophosphatidic acid, polyamines ( e.g . spermine, spermidine, and putrescine) and conjugates of biogenic amines ( e.g . N- arachidonylethanolamine (anandamide), N- arachidonoyldopamine (NADA), N- oleoyldopamine, N-oleoylethanolamine (OLEA), N-arachidonolylserine, N- hexadecanamide, and various N-acyltaurines and N-acylsalsolinols) TRPV4 Bisandrographolide A (BAA), alpha- phorbol 12,13-didecanoate (4 α - PDD), phorbol 12-myristate 13- acetate (4 α -PDH), apigenin, GSK1016790A and RN1747 Mechanical and thermal (>24°C) Citric acid, dimethylallyl pyrophosphate, anandamide, arachidonic acids and epoxyeicosatrienoic acid metabolites ( e.g . 5,6-epoxyeicosatrienoic acid (5,6-EET) and 8,9-EET, which also mediate TRPV4 activation by cell swelling) TRPA1 Allyl isothiocyanate (AITC), cinnamaldehyde (cinnamon), allicin (garlic), carvacrol and thymol (oregano), curcumin (turmeric), capsiate (capsinoid), acrolein, menthol, icilin, nicotine, URB597, chlorobenzylidene malononitrile (tear gas), formalin, α , β -unsaturated aldehydes, auranofin, PF-4840154, cannabichromene, cannabidiol (CBD), tetrahydrocannabinol (THC) and apomorphine (agonist in low micromolar range and antagonist in higher concentration) Mechanical and thermal (<15°C and >25°C) Prostaglandins ( e.g . prostaglandin A1, 8-iso- prostaglandin A2, and 15-deoxy-∆- prostaglandin J2), 4-Hydroxnonenal (4- HNE, a lipid peroxidation product), 4- oxononenal (4-ONE), methylglyoxal, reactive oxygen species (ROS), cytokines ( e.g . TNF- α and IL-6), bradykinin and hydrogen sulphide TRPM8 Menthol, icilin, linalool, geraniol, WS- 3, WS-12, WS-23, PMD38, hydroxycitronellal, FrescolatMGA, FrescolatML, CoolactP, Cooling Agent 10, cis- and trans-p- menthane3 and CPS-36 Thermal (<28°C) Unknown