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SENTINEL MOLECULE. "The non-selective cation channel TRPA1...is perhaps the most versatile of all polymodal sensory ion channels. Different TRPA1 orthologues were reported to mediate the detection of cold, heat and noxious chemicals, such as allyl isothiocyanate (AITC), the pungent agent from wasabi and other mustard plants." https://lnkd.in/eFfEp_R View in LinkedIn

MANY ACTIVATORS. "TRPA1 can also be activated by endogenous metabolic products and oxidative stress-derived substances and sensitized through G protein-coupled receptors (GPCRs), cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), and protease activated receptor 2 (PAR2) signaling pathways." https://lnkd.in/ecaVp5Q View in LinkedIn

MANY ACTIVATORS. "TRPA1 is activated by a variety of chemical compounds, such as allyl isothiocyanate in mustard oil (MO), allicin in garlic and onion, and synthetic drugs such as clotrimazole, chlorpromazine, and clioquinol." https://lnkd.in/ecaVp5Q View in LinkedIn

RADS, ASTHMA, COPD. "In addition to directly activating a cough reflex, TRPA1 ligands may also be involved in the hypersensitization of cough and other sensory reflexes." https://lnkd.in/ey47aVM View in LinkedIn

CAPSAICIN LINK. "The capsaicin- and heat-activated non-selective cation channel TRPV1 exhibits robust temperature activation above 42°C in heterologous systems and primary neurons...TRPV1-deficient mice show complete loss of capsaicin sensitivity and significant reduction in the detection of noxious (≥50°C) heat stimuli and/or thermal hyperalgesia." Similarly, birds are oblivious to capsaicin. https://lnkd.in/eFfEp_R View in LinkedIn

DIVERSE ACTIVATORS AND OUTCOMES. "TRPA1 was found to be activated by a variety of chemical compounds, including mustard oil and cannabinoids. Subsequent studies identified additional ligands and revealed roles in pain, inflammation, itch, mechanical sensation, oxygen regulation, and more." https://lnkd.in/e-WBvC9 View in LinkedIn

MOLECULAR MAPPING. "The molecular determinants of temperature sensing in TRPV1 have been located in the N terminal domain in the pore turret, in the outer pore region, and in the C terminal. TRPV1 and TRPV2... are heat receptors with different temperature thresholds and share an amino acid identity of about 70%." https://lnkd.in/eZQCjnY View in LinkedIn

TOXINEERING. "The researchers identified a tarantula spider peptide, protoxin-I, as the first high-affinity peptide antagonist of the transient receptor potential ankyrin 1 (TRPA1) channel. Nitabach’s team also used toxineering to create a novel protoxin-I mutant with improved specificity for TRPA1, underscoring the value of the approach for pharmaceutical discovery." https://lnkd.in/eQA7Yck View in LinkedIn

"ACTIVATION in temperature-sensitive TRP channels is characterized by very large enthalpy changes that are compensated by similarly large entropy changes. For example, enthalpy changes of about 100 kcal/mol, 200 kcal/mol, and 60 kcal/mol are involved in the opening of TRPV1, TRPV2, and TRPM8, respectively." https://lnkd.in/eZQCjnY View in LinkedIn

VENOM PAYLOAD. "A key issue in ion channel toxin biology has been the mining of this great pharmacological diversity—e.g., spiders alone are estimated to collectively contain millions of distinct peptide toxins in their venoms —to identify toxins with high affinity for particular ion channel targets." https://lnkd.in/ecaVp5Q View in LinkedIn