Pharmacology, Toxicology and Environmental Health Commons^™

A Study Of Trpa1 Activation Via Covalent Electrophilic Modification Of Cysteines, Thomas A. Parks

USF Tampa Graduate Theses and Dissertations

A subset of sensory nerves called nociceptors are stimulated by noxious stimuli and evoke nocifensive responses in different organ systems. Transient Receptor Potential Ankyrin 1 (TRPA1) is a tetrameric, nonselective, cation channel that initiates the generator potential that evokes afferent signaling in nociceptive nerves. TRPA1 is activated many harmful irritants, such as food chemicals, environmental pollutants, reactive oxygen species and other endogenous mediators. Most TRPA1 agonists have electrophilic properties, which covalently modify cysteine residues on the cytosolic side of the channel. Biochemical studies in our lab have identified four cysteines (C273, C621, C665, C1085) that rapidly bound iodoacetamide (irreversible electrophile); …