Segmental differences in the non-neuronal cholinergic system in rat caecum.

Acetylcholine is not only a neurotransmitter but is also produced by several non-neuronal cell types with barrier or defence function. One of the non-neuronal tissues with expression of the key enzyme for production of acetylcholine, the choline acetyltransferase (ChAT), is the colonic surface epithelium, which releases acetylcholine after contact with the short-chain fatty acid propionate produced physiologically in the colonic lumen during the microbial fermentation of carbohydrates. Despite the fact that the caecum is the largest fermentation chamber in non-ruminant mammals, nothing is known about the expression and function of a non-neuronal cholinergic system in this part of the large intestine, which was addressed in the present study. In Ussing chamber experiments, propionate induced a concentration-dependent Cl secretion leading to an increase in short-circuit current (I), which was stronger in the aboral part (near the blind ending sac of the caecum) compared to the oral part of caecum. The propionate-induced I was blocked by atropine, but was resistant against tetrodotoxin, conotoxins (MVIIC and SVIB) or hexamethonium indicating that propionate acts via non-neuronal acetylcholine. Immunohistochemical staining revealed the expression of ChAT in the caecal surface epithelium with a significant gradient between aboral (high) and oral (low) expression. This difference combined with a higher efficiency of cholinergically induced anion secretion (as revealed by the I evoked by the cholinergic agonist carbachol) is probably responsible for the segment dependency of the response to propionate. In summary, propionate stimulates anion secretion in rat caecum via non-neuronal acetylcholine emphasizing the physiological importance of the non-neuronal cholinergic system in the communication between the gastrointestinal microbiome and the mammalian host.