TRP channel functions in the gastrointestinal tract

Abstract

Transient receptor potential (TRP) channels are predominantly distributed in both somatic and visceral sensory nervous systems and play a crucial role in sensory transduction. As the largest visceral organ system, the gastrointestinal (GI) tract frequently accommodates external inputs, which stimulate sensory nerves to initiate and coordinate sensory and motor functions in order to digest and absorb nutrients. Meanwhile, the sensory nerves in the GI tract are also able to detect potential tissue damage by responding to noxious irritants. This nocifensive function is mediated through specific ion channels and receptors expressed in a subpopulation of spinal and vagal afferent nerve called nociceptor. In the last 18 years, our understanding of TRP channel expression and function in GI sensory nervous system has been continuously improved. In this review, we focus on the expressions and functions of TRPV1, TRPA1, and TRPM8 in primary extrinsic afferent nerves innervated in the esophagus, stomach, intestine, and colon and briefly discuss their potential roles in relevant GI disorders.

Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease

“…Transient receptor potential vanilloid 1 is a molecular integrator of signaling pathways for multiple types of sensory agents, including chemical, thermal, and endogenous mediators . Deregulation of the physiological function of this receptor, eg, through overexpression or uncontrolled sensitization, is critical in the etiology of GI diseases, including GERD . Esophageal TRPV1 expression has been analyzed in preclinical and clinical studies.…”

“…21 Deregulation of the physiological function of this receptor, eg, through overexpression or uncontrolled sensitization, is critical in the etiology of GI diseases, including GERD. 22 Esophageal TRPV1 expression has been analyzed in preclinical and clinical studies. In patients with reflux symptoms, the acid exposure is associated with increased TRPV1 immunoreactivity in biopsies from esophageal mucosa.…”

Gastric administration of garlic powder containing the trpa1‐ agonist allicin induces specific epigastric symptoms and gastric relaxation in healthy subjects

“…However, higher doses of allicin induced profound nausea and vomitus, symptoms that are not observable even after application of the highest tolerable doses of capsaicin . Moreover, the sensory responses elicited by allicin may also be the result of a complex interaction between TRPA1 and TRPV1 on sensory nerve endings and not solely through TRPA1 excitation, as both channels have been shown to interact with each other …”

“…In summary, we have characterized the perception induced by gastric stimulation of TRPA1 in vivo and have shown a profound relaxation in response to TRPA1 stimulation. Given its known involvement in mechanical and inflammatory pain and in priming visceral hypersensitivity, this polymodal ion channel may be a novel target for the diagnosis and therapy of visceral pain . The future use of compounds less volatile than allicin may allow longer observation periods and the study of long term and repeated TRPA1 stimulation.…”

Effects of ginger constituent 6‐shogaol on gastroesophageal vagal afferent C‐fibers

“…Among them, TRPV1 is activated by capsaicin in hot peppers, TRPA1 can be activated by isothiocyanate in horseradish, cinnamaldehyde in cinnamon, and thiosulfinates in garlic, and TRPM8 is responsible for the “cooling” sensation of menthol in peppermint . Our previous studies have systemically addressed those pungent compounds‐induced actions on the TRP channels in vagal nociceptive C‐fiber subtypes in the gastrointestinal (GI) tract …”