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Free fatty acid receptor 3 activation suppresses neurogenic motility in rat proximal colon
Author(s) -
Kaji I.,
Akiba Y.,
Furuyama T.,
Adelson D. W.,
Iwamoto K.,
Watanabe M.,
Kuwahara A.,
Kaunitz J. D.
Publication year - 2018
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13157
Subject(s) - myenteric plexus , bethanechol , cholinergic , endocrinology , medicine , nicotinic agonist , acetylcholine , chemistry , serotonin , agonist , enteric nervous system , receptor , biology , muscarinic acetylcholine receptor , immunohistochemistry
Abstract Background Short‐chain fatty acids ( SCFA ) are microbial fermentation products absorbed by the colon. We recently reported that activation of the SCFA receptor termed free fatty acid receptor 3 ( FFA 3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor ( nAChR )‐mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed FFA 3 affects colonic motor function. Methods FFA 3‐expressing myenteric neurons were identified by immunostaining; contractions of isolated circular muscle strips obtained from rat proximal colon were measured by isometric transducers. The effect of FFA 3 agonists on defecation in vivo was examined in an exogenous serotonin‐induced defecation model. Key Results FFA 3 immunoreactivity was located in nitrergic and cholinergic neurons in the myenteric plexus. In isolated circular muscle strips without mucosa and submucosa, the addition of nicotine (10 μM) or serotonin transiently relaxed the muscle through nitrergic neurons, whereas high concentrations of nicotine (100 μM) induced large‐amplitude contractions that were mediated by cholinergic neurons. Pretreatment with FFA 3 agonists inhibited nicotine‐ or serotonin‐induced motility changes but had no effect on bethanechol‐induced direct muscle contractions. The G i/o inhibitor pertussis toxin reversed the inhibitory effect of an FFA 3 agonist AR 420626 on nicotine‐evoked contractions, suggesting that FFA 3 activation suppresses nAChR ‐mediated neural activity in myenteric neurons, consistent with an FFA 3‐mediated antisecretory effect. In conscious rats, exogenous serotonin increased the volume of fecal output, compared with the vehicle‐ or AR 420626‐treated groups. Pretreatment with AR 420626 significantly suppressed serotonin‐induced fecal output. Conclusion and Inferences FFA 3 is a promising target for the treatment of neurogenic diarrheal disorders by suppressing nAChR ‐mediated neural pathways.