Abstract
Propionate, a metabolite from the microbial fermentation of carbohydrates, evokes a release of epithelial acetylcholine in rat caecum resulting in an increase of short-circuit current (Isc) in Ussing chamber experiments. The present experiments were performed in order to characterize the ionic mechanisms underlying this response which has been thought to be due to Cl− secretion. As there are regional differences within the caecal epithelium, the experiments were conducted at oral and aboral rat corpus caeci. In both caecal segments, the propionate-induced Isc (IProp) was inhibited by > 85%, when the experiments were performed either in nominally Cl−- or nominally HCO3−-free buffer. In the case of Cl−, the dependency was restricted to the presence of Cl− in the serosal bath. Bumetanide, a blocker of the Na+-K+-2Cl−-cotransporter, only numerically reduced IProp suggesting that a large part of this current must be carried by an ion other than Cl−. In the aboral caecum, IProp was significantly inhibited by mucosally administered stilbene derivatives (SITS, DIDS, DNDS), which block anion exchangers. Serosal Na+-free buffer reduced IProp significantly in the oral (and numerically also in aboral) corpus caeci. RT-PCR experiments revealed the expression of several forms of Na+-dependent HCO3−-cotransporters in caecum, which might underlie the observed Na+ dependency. These results suggest that propionate sensing in caecum is coupled to HCO3– secretion, which functionally would stabilize luminal pH when the microbial fermentation leads to an increase in the concentration of short-chain fatty acids in the caecal lumen.
Highlights
The caecum, forming a blind sac interconnected between the ileum and the colon, is the largest fermentation chamber of herbivorous or omnivorous non-ruminant animals
As many C l− secreting pathways such as the dominant anion channel in the apical membrane of intestinal epithelial cells, the CFTR channel, are permeable for HCO3− [24], it seems to be of interest to study whether HCO3− contributes to the electrogenic response evoked by luminal propionate in the caecum
The prerequisite for Cl− secretion across apical anion channels is the intracellular accumulation of this anion above its electrochemical equilibrium, a process which is generally mediated by secondary active basolateral Cl− uptake via the Na+-K+-2Cl–-cotransporter type 1 (NKCC1; [12])
Summary
The caecum, forming a blind sac interconnected between the ileum and the colon, is the largest fermentation chamber of herbivorous or omnivorous non-ruminant animals. Its pendant in ruminant species is the forestomach system, in which large amounts of short-chain fatty acids are produced and absorbed by the epithelium serving as an energy source for the host, i.e., the mammal. An increase in the production of short-chain fatty acids (induced experimentally by intraruminal application of highly digestible carbohydrates) in the forestomach system increases salivary secretion [28]. This HCO3−-rich fluid serves as a buffer necessary to prevent an acidification of the lumen of the forestomach, which would disturb the complex microbial ecosystem in this fermentation chamber leading to a potentially lethal disease, i.e., ruminal acidosis [4]. As rat caecum exhibits large segmental differences in basal ion transport and in the epithelial expression of choline acetyltransferase (ChAT), the key enzyme for the production of acetylcholine [6], we tried to find out in the present study if H CO3− transport contributes to propionate-induced anion secretion in rat oral and aboral corpus caeci
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