Endogenous Modulators of TRP Channels

Enza      Palazzo; Francesco      Rossi; Vito      de Novellis; Sabatino      Maione

Abstract

The transient receptor potential (TRP) superfamily consists of a large number of cation channels permeable to both monovalent and divalent cations. The 28 mammalian TRP channels can be divided into seven subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), TRPN (no mechanopotential, NOMP) and the TRPA (ankyrin) groups. TRP channels are widely expressed in several cell types in every tissue and play a critical role in the regulation of various cell functions. Altogether these channels function as sensory transducers and detect chemical, thermal and mechanical stimuli. Endogenous substances acting on TRP channels can be released during the early stage of some pathological conditions. These substances can affect TRP channel functions and lead to the progression of diseases such as inflammation and chronic pain. For example, endogenous lipids, such as unsaturated fatty acids and their cyclooxygenase, lipoxygenase or epoxygenase related metabolites, were shown to modulate TRP channel activity by direct binding. Other lipidergic ligands include isoprene derivatives (e.g. diacylglycerol, lysophospholipids and resolvine) which play diverse activity on different TRP channels. This review focuses on lipidergic mediators which affect TRP channel activity. Opportunities to exploit TRP channels for novel therapeutic strategies will be discussed.

Keywords: Endogenous TRP ligands, neurogenic inflammation cascade, pain sensitization, TRPV1 desentization, peripheral sensory neurons

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