TY  - JOUR
A1  - Schütz, Burkhard
A1  - Jurastow, Innokentij
A1  - Bader, Sandra
A1  - Ringer, Cornelia
A1  - Engelhardt, Jakob von
A1  - Chubanov, Vladimir
A1  - Gudermann, Thomas
A1  - Diener, Martin
A1  - Kummer, Wolfgang
A1  - Krasteva-Christ, Gabriela
A1  - Weihe, Eberhard
T1  - Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract
JF  - Frontiers in Physiology
N2  - 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 (EGFP\(^{ChAT}\)) and by using in situ hybridization and immunohistochemistry we found that EGFP\(^{ChAT}\) cells were clustered in the epithelium lining the gastric groove. EGFP\(^{ChAT}\) cells were numerous in the gall bladder and bile duct, and found scattered as solitary cells along the small and large intestine. While all EGFP\(^{ChAT}\) cells were also ChAT-positive, expression of the high-affinity choline transporter (ChT1) was never detected. Except for the proximal colon, EGFP\(^{ChAT}\) cells also lacked detectable expression of the vesicular acetylcholine transporter (VAChT). EGFP\(^{ChAT}\) 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 EGFP\(^{ChAT}\) 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, EGFP\(^{ChAT}\) 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.
KW  - vesicular acetylcholine transporter
KW  - nonneuronal acetylcholine
KW  - nervous system
KW  - functional characterization
KW  - cholinergic
KW  - taste receptor cells
KW  - enteroendocrine cells
KW  - gene locus
KW  - tuft cells
KW  - transgenic mice
KW  - expression
KW  - brush cell
KW  - ChAT
KW  - VAChT
KW  - ChT1
KW  - intestine
KW  - gall bladder
KW  - bile duct
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143550
VL  - 6
IS  - 87
ER  - 
TY  - JOUR
A1  - Hollenhorst, Monika I.
A1  - Jurastow, Innokentij
A1  - Nandigama, Rajender
A1  - Appenzeller, Silke
A1  - Li, Lei
A1  - Vogel, Jörg
A1  - Wiederhold, Stephanie
A1  - Althaus, Mike
A1  - Empting, Martin
A1  - Altmüller, Janine
A1  - Hirsch, Anna K. H.
A1  - Flockerzi, Veit
A1  - Canning, Brendan J.
A1  - Saliba, Antoine‐Emmanuel
A1  - Krasteva‐Christ, Gabriela
T1  - Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling
JF  - The FASEB Journal
N2  - For protection from inhaled pathogens many strategies have evolved in the airways such as mucociliary clearance and cough. We have previously shown that protective respiratory reflexes to locally released bacterial bitter “taste” substances are most probably initiated by tracheal brush cells (BC). Our single‐cell RNA‐seq analysis of murine BC revealed high expression levels of cholinergic and bitter taste signaling transcripts (Tas2r108, Gnat3, Trpm5). We directly demonstrate the secretion of acetylcholine (ACh) from BC upon stimulation with the Tas2R agonist denatonium. Inhibition of the taste transduction cascade abolished the increase in [Ca\(^{2+}\)]\(_{i}\) in BC and subsequent ACh‐release. ACh‐release is regulated in an autocrine manner. While the muscarinic ACh‐receptors M3R and M1R are activating, M2R is inhibitory. Paracrine effects of ACh released in response to denatonium included increased [Ca\(^{2+}\)]\(_{i}\) in ciliated cells. Stimulation by denatonium or with Pseudomonas quinolone signaling molecules led to an increase in mucociliary clearance in explanted tracheae that was Trpm5‐ and M3R‐mediated. We show that ACh‐release from BC via the bitter taste cascade leads to immediate paracrine protective responses that can be boosted in an autocrine manner. This mechanism represents the initial step for the activation of innate immune responses against pathogens in the airways.
KW  - acetylcholine
KW  - brush cells
KW  - mucociliary clearance
KW  - single‐cell RNA‐seq
KW  - taste
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213516
VL  - 34
IS  - 1
SP  - 316
EP  - 332
ER  -