Neural anti-inflammatory action mediated by two types of acetylcholine receptors in the small intestine
2019
Gastrointestinal
prokinetic agentsfunction as serotonin-4 receptor (5-HT4R) agonists to activate
myenteric plexusneurons to release acetylcholine (ACh), which then induce
anti-inflammatoryaction. Details of this pathway, however, remain unknown. The aim of this study is to clarify the
anti-inflammatorymechanism underlying the 5-HT4R agonist,
mosapride citrate(MOS)-induced
anti-inflammatoryaction on
postoperative ileus(POI). POI models were generated from wild-type C57BL6/J (WT), 5-HT4R knock-out (S4R KO), α7 nicotinic AChR KO (α7 R KO), and M2 muscarinic ACh receptor KO (M2R KO) mice. MOS attenuated leukocyte infiltration in WT. MOS-induced
anti-inflammatoryaction was completely abolished in both S4R KO and S4R KO mice upon wild-type bone marrow transplantation. MOS-induced
anti-inflammatoryaction against macrophage infiltration, but not neutrophil infiltration, was attenuated in α7 R KO mice. Selective α7nAChR agonists (PNU-282987 and
AR-R17779) also inhibited only macrophage infiltration in POI. MOS-mediated inhibition of neutrophil infiltration was diminished by atropine, M2AChR antagonist,
methoctramine, and in M2R KO mice. Stimulation with 5-HT4R inhibits leukocyte infiltration in POI, possibly through
myenteric plexusactivation. Released ACh inhibited macrophage and neutrophil infiltration likely by activation of α7nAChR on macrophages and M2AChR. Thus, macrophage and neutrophil recruitment into inflamed sites is regulated by different types of AChR in the small intestine.
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