Abstract
The transient receptor potential (TRP) channels superfamily are a large group of proteins that play crucial roles in cellular processes. For example, these cation channels act as sensors in the detection and transduction of stimuli of temperature, small molecules, voltage, pH, and mechanical constrains. Over the past decades, different members of the TRP channels have been identified in the human gastrointestinal (GI) tract playing multiple modulatory roles. Noteworthy, TRPs support critical functions related to the taste perception, mechanosensation, and pain. They also participate in the modulation of motility and secretions of the human gut. Last but not least, altered expression or activity and mutations in the TRP genes are often related to a wide range of disorders of the gut epithelium, including inflammatory bowel disease, fibrosis, visceral hyperalgesia, irritable bowel syndrome, and colorectal cancer. TRP channels could therefore be promising drug targets for the treatment of GI malignancies. This review aims at providing a comprehensive picture of the most recent advances highlighting the expression and function of TRP channels in the GI tract, and secondly, the description of the potential roles of TRPs in relevant disorders is discussed reporting our standpoint on GI tract–TRP channels interactions.
Highlights
The primary function of the gastrointestinal (GI) tract is the transport, digestion, and absorption of nutrients and liquids
This review aims at providing a comprehensive picture of the most recent advances highlighting the expression and function of transient receptor potential (TRP) channels in the GI tract, and secondly, the description of the potential roles of TRPs in relevant disorders is discussed reporting our standpoint on GI tract–TRP channels interactions
TRP channels act as molecular sensors of multiple and specific stimuli, for example, they can be gated by temperature, either heat (e.g., TRPV1) or cold (e.g., TRPA1 and TRPM8), taste, pH, osmolality, mechanical forces, bioactive substances, and by several natural and artificial ligands including pungent and cooling agents, fragrant components, dietary ingredients, environmental irritants, noxious substances, and inflammatory mediators [13,14,15]
Summary
The primary function of the gastrointestinal (GI) tract is the transport, digestion, and absorption of nutrients and liquids. TRP channels act as molecular sensors of multiple and specific stimuli, for example, they can be gated by temperature, either heat (e.g., TRPV1) or cold (e.g., TRPA1 and TRPM8), taste, pH, osmolality, mechanical forces, bioactive substances (e.g., neurotransmitters and hormones), and by several natural and artificial ligands including pungent and cooling agents, fragrant components, dietary ingredients (e.g., chemicals and metabolites), environmental irritants, noxious substances, and inflammatory mediators [13,14,15] These exogenous and/or local endogenous stimuli activate channels leading to plasma membrane depolarization and, eventually, to Ca2+ influx which prompts several signal transduction mechanisms (e.g., action potentials) which reach the autonomous and central nervous system, causing reflex responses and sensations [16,17]. We summarize what is known on the involvement of TRPs in GI diseases/disorders and the potential use of pharmacological regulators in the treatment of these malignancies
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