4.1 TRPA1 in the gastrointestinal tract: General functions
including ion transport, gastric emptying
As discussed earlier, TRPA1 is highly expressed in the gastrointestinal
tract, distributed from stomach to colon. TRPA1 is found to be present
in the enterochromaffin cells (EC cells), enteroendocrine cells of the
intestine but not in the smooth layers or submucosal layers of the
intestine(Nozawa et al.. 2009). Endocrine cells of the gut including
enterochromaffin cells secrete neurotransmitters and hormones that
regulate various gastrointestinal functions. One of the
neurotransmitters that has been found to regulate the gastric motility
and contractions is serotonin or 5-HT. It is also stored in
enterochromaffin cells throughout the gut and is involved in the
excitation of both intrinsic and extrinsic neurons, resulted in the
modulation of many gastrointestinal functions (Gershon & Tack, 2007).
TRPA1 agonist acrolein, AITC and cinnamaldehyde has been reported to
stimulate the release of 5-HT from freshly isolated EC cells and RIN14B
cell line(Nozawa et al., 2009). Similar studies with other TRPA1
agonists like methyl salicylate, eugenol, hypotonic solution and cold
temperature stimulated the release of 5-HT from the EC cell, implicating
its potential role in the regulation of gastric motility. Thesein-vitro studies were further supported by in-vivo effect
of TRPA1 agonists like AITC, eugenol, thymol on gastric delaying through
activation of the serotonergic pathway to stimulate the release of 5-HT
from intestinal EC cells and mast cells(Doihara et al. 2009). These
studies cumulatively showed that TRPA1 can act as luminal sensor in the
intestine and could be used as a therapeutic target to regulate gastric
motility.
TRPA1 expression in enterocytes of the duodenum and colon of mice also
facilitates mucosal ion transport. TRPA1 agonists like AITC,
cinnamaldehyde and linalool when applied to the luminal surface of
duodenum and colon of the mice, stimulated short circuit ion current in
the membrane. These experiments suggested the role of TRPA1 activation
in the transepithelial ion transport, which has been linked to the fluid
movement across the epithelium in the intestine. Also, there was no
response in the presence of TRPA1 antagonists as well as in the TRPA1
knockout mice. Therefore, the presence of TRPA1 within the enterocytes
is of great importance in terms of the absorption of nutrients from the
intestine(Fothergill et al. 2016).