Robustness of the non-neuronal cholinergic system in rat large intestine against luminal challenges

Long-Chain Acylcholines Link Butyrylcholinesterase to Regulation of Non-neuronal Cholinergic Signaling

“…While not the primary focus of this review, several links between acylcholines and microbial metabolism have been suggested, though mechanistic studies are still needed to understand effects. For example, two recent studies have shown production of propionylcholine and butyrylcholine in response to short-chain fatty acids. , Direct production of acetylcholine by L. plantarum , a strain used in probiotic formulations, has also been described, though whether this is bioavailable to neurons in the gut is uncertain.…”

“…Historical studies have suggested the short-chain acylcholines, propionylcholine and butyrylcholine, have cholinergic signaling properties mimicking acetylcholine. , Recent studies have identified production of these compounds at several sites, for example, in the gut epithelium where propionylcholine and butyrylcholine, along with acetylcholine, have been shown to be locally produced. Whereas acetylcholine stimulates ionic current leading to muscle contraction and epithelial transport, propionylcholine and butyrylcholine desensitize cholinergic signaling and reduce ionic current in response to acetylcholine by up to half–leading to the proposal that butyrylcholine and propionylcholine are modulators of cholinergic signaling influenced by the level of short-chain fatty acids produced by gut microbiota. , Compounds closely related to acylcholines–dicarboxylic acid mono- and dicholines–have been used for decades as neuromuscular blockers that bind to and desensitize acetylcholine receptors at the neuromuscular junction. The most notable member of this class, succinylcholine, is a fast onset muscle relaxant.…”

Evidence for tetrodotoxin‐resistant spontaneous myogenic contractions of mouse isolated stomach that are dependent on acetylcholine

“…Non‐neuronal sources of ACh are found in gastro‐oesophageal epithelia and gastrointestinal immune cells, including tuft cells (Beckmann & Lips, 2013 ; Cox et al, 2020 ; Grando et al, 2020 ; Schneider et al, 2019 ; Wessler & Kirkpatrick, 2008 ; Wolf‐Johnston et al, 2012 ). The rat colonic epithelium is also a non‐neuronal source of ACh, which is implicated in the regulation of ionic transport and proposed to be an interface between the colonic microbiome and the host (Bader et al, 2019 ; Bader & Diener, 2018 ). In addition, intramuscular ICCs may be a source of paracrine substances, based on constitutive expression of COX‐2 (Porcher et al, 2002 ).…”

Unravelling the secrets of the caecum

“…Building on two previous studies published in Pflügers Arch. [1,2], in the current issue, Pouokam and Diener systematically compare differences in ion transport across two different segments of the rat caecum [8]. As in the classical model, a basolateral NKCC drives secretion via anion channels, possibly delivering HCO 3…”