ArticleGut2004
Intracellular potentiation between two second messenger systems may contribute to cholera toxin induced intestinal secretion in humans.
Article in Gut, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Potassium channels in intestinal epithelial cells and their pharmacological modulation: a systematic review.American journal of physiology. Cell physiology · 2021Pooled it
- Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.PloS one · 2022Article
- Cholinergic Submucosal Neurons Display Increased Excitability FollowingFrontiers in physiology · 2018Article
- Early life adversity in piglets induces long-term upregulation of the enteric cholinergic nervous system and heightened, sex-specific secretomotor neuron responses.Neurogastroenterology and motility · 2016Article
- Simultaneous exposure to Escherichia coli heat-labile and heat-stable enterotoxins increases fluid secretion and alters cyclic nucleotide and cytokine production by intestinal epithelial cells.Infection and immunity · 2014Article
- Properties of cholinergic and non-cholinergic submucosal neurons along the mouse colon.The Journal of physiology · 2014Article
- Cholinergic regulation of epithelial ion transport in the mammalian intestine.British journal of pharmacology · 2006Review
- Ultrastructural changes in the Meissner plexus of the suckling rabbit small intestine in experimental cholera.Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sectionsArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCholera toxin (CT) acts on intestinal epithelial cells both directly and indirectly via activation of a secretory neural reflex. The reflex may release acetylcholine as one of its final neurotransmitters. This opens up the possibility of a third mechanism of action for CT, namely a synergistic interaction between two secretagogues acting on different second messenger systems within the epithelial cell.
aimsTo establish evidence for cholinergic innervation to human ileal epithelial cells and to investigate whether CT potentiates the action of acetylcholine on human intestinal epithelial cells.
methodsTransverse sections of human ileum were examined for mucosal cholinergic nerves and M3 muscarinic receptors using antibodies raised to choline acetyltransferase and M3 receptors. Short circuit current (Isc) responses and ion flux movements were elicited from T84 epithelial cell monolayers set up in Ussing chambers.
resultsImmunohistochemistry of native human ileal mucosa revealed the presence of both cholinergic nerves and muscarinic M3 receptors located to the basolateral domain of epithelial cells. Secretory responses of T84 cell monolayers to acetylcholine were greatly potentiated in the presence of CT. This effect, substituting forskolin for CT, was mirrored by increases in basolateral 86Rb and apical 125I efflux. Charybdotoxin plus apamin reduced both Isc and 86Rb efflux evoked by acetylcholine, in the presence of forskolin.
conclusionsHuman ileal mucosa receives a direct cholinergic innervation to its epithelial cells. Secretory effects of acetylcholine on epithelial cells are augmented in the presence of CT. Such a synergistic response is dependent on optimum opening of basolateral potassium channels by acetylcholine and apical chloride channels by CT. The interaction may contribute to the mechanism of action of cholera toxin induced secretory diarrhoea.
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