We have located links that may give you full text access.
Free fatty acid receptor 3 activation suppresses neurogenic motility in rat proximal colon.
Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society 2018 January
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 (FFA3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor (nAChR)-mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed FFA3 affects colonic motor function.
METHODS: FFA3-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 FFA3 agonists on defecation in vivo was examined in an exogenous serotonin-induced defecation model.
KEY RESULTS: FFA3 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 FFA3 agonists inhibited nicotine- or serotonin-induced motility changes but had no effect on bethanechol-induced direct muscle contractions. The Gi/o inhibitor pertussis toxin reversed the inhibitory effect of an FFA3 agonist AR420626 on nicotine-evoked contractions, suggesting that FFA3 activation suppresses nAChR-mediated neural activity in myenteric neurons, consistent with an FFA3-mediated antisecretory effect. In conscious rats, exogenous serotonin increased the volume of fecal output, compared with the vehicle- or AR420626-treated groups. Pretreatment with AR420626 significantly suppressed serotonin-induced fecal output.
CONCLUSION AND INFERENCES: FFA3 is a promising target for the treatment of neurogenic diarrheal disorders by suppressing nAChR-mediated neural pathways.
METHODS: FFA3-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 FFA3 agonists on defecation in vivo was examined in an exogenous serotonin-induced defecation model.
KEY RESULTS: FFA3 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 FFA3 agonists inhibited nicotine- or serotonin-induced motility changes but had no effect on bethanechol-induced direct muscle contractions. The Gi/o inhibitor pertussis toxin reversed the inhibitory effect of an FFA3 agonist AR420626 on nicotine-evoked contractions, suggesting that FFA3 activation suppresses nAChR-mediated neural activity in myenteric neurons, consistent with an FFA3-mediated antisecretory effect. In conscious rats, exogenous serotonin increased the volume of fecal output, compared with the vehicle- or AR420626-treated groups. Pretreatment with AR420626 significantly suppressed serotonin-induced fecal output.
CONCLUSION AND INFERENCES: FFA3 is a promising target for the treatment of neurogenic diarrheal disorders by suppressing nAChR-mediated neural pathways.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app