Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract

Abstract

The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline acetyltransferase (ChAT)-positive brush cells with taste cell-like traits. With the aid of two transgenic mouse lines that express green fluorescent protein (EGFP) under the control of the ChAT promoter (EGFPChAT) and by using in situ hybridization and immunohistochemistry we found that EGFPChAT cells were clustered in the epithelium lining the gastric groove. EGFPChAT cells were numerous in the gall bladder and bile duct, and found scattered as solitary cells along the small and large intestine. While all EGFPChAT cells were also ChAT-positive, expression of the high-affinity choline transporter (ChT1) was never detected. Except for the proximal colon, EGFPChAT cells also lacked detectable expression of the vesicular acetylcholine transporter (VAChT). EGFPChAT cells were found to be separate from enteroendocrine cells, however they were all immunoreactive for cytokeratin 18 (CK18), transient receptor potential melastatin-like subtype 5 channel (TRPM5), and for cyclooxygenases 1 (COX1) and 2 (COX2). The ex vivo stimulation of colonic EGFPChAT cells with the bitter substance denatonium resulted in a strong increase in intracellular calcium, while in other epithelial cells such an increase was significantly weaker and also timely delayed. Subsequent stimulation with cycloheximide was ineffective in both cell populations. Given their chemical coding and chemosensory properties, EGFPChAT brush cells thus may have integrative functions and participate in induction of protective reflexes and inflammatory events by utilizing ACh and prostaglandins for paracrine signaling.

Taste buds: cells, signals and synapses

“…The implication of this is that ingested nutrients and non-nutrient chemicals (such as glucose, peptides, amino acids, bitter compounds, fats and, possibly, the fermentation products of gut microbiota) stimulate taste receptors on gut cells to elicit various defence mechanisms and/or the secretion of appetite-regulating hormones 98, 203, 204 . Chemicals in the gastrointestinal lumen may also provoke SCCs to release transmitters — possibly acetylcholine 206 — that act in a paracrine manner on neighbouring enteroendocrine cells.…”

Intestinal tuft cells regulate the ATM mediated DNA Damage response via Dclk1 dependent mechanism for crypt restitution following radiation injury

“…These cells have unique morphology and express Dclk1 and several additional unique proteins, including Cox-1, Cox-2, and trpm51819. Recent evidence suggests that tuft cells are chemosensory cells that capture locally transmitted microenvironmental signals that may regulate the secretory response governing cell fate during injury and, perhaps, homeostasis2021. Very recently, we identified the molecular signature of Dclk1 expressing intestinal epithelial tuft cells, which display the hallmarks of quiescence and self-renewal22.…”

Luminal chemosensing in the gastroduodenal mucosa

“…Electron microscopy identified tuft cells morphologically by long apical microvilli, narrow rootlets, and well-developed tublovesicular structures in the cytoplasm. Tuft cells are present throughout GI tract, including in salivary and bile ducts [33]; they express many bioactive molecules, such as nitric oxide in rat stomach [34], ACh in mouse stomach [35], guanylin in human duodenum, but not in rat duodenum [36*], opioids, uroguanylin, and prostaglandins in mouse duodenum [37;38]. Since tuft cells lack chromogranin-positive granules, they may synthesize transmitters de novo, releasing them predominantly into the lumen.…”