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dc.contributor.authorSia, TC
dc.contributor.authorFlack, N
dc.contributor.authorRobinson, L
dc.contributor.authorKyloh, Melinda
dc.contributor.authorNicholas, Sarah J
dc.contributor.authorBrookes, Simon Jonathan
dc.contributor.authorWattchow, David Anthony
dc.contributor.authorDinning, Phillip
dc.contributor.authorOliver, John Reginald
dc.contributor.authorSpencer, Nicholas John
dc.identifier.citationSia, T.C., Flack, N., Robinson, L., Kyloh, M., Nicholas, S.J., Brookes, S.J., Wattchow, D.A., Dinning, P., Oliver, J. and Spencer, N.J., 2013. Is serotonin in enteric nerves required for distension-evoked peristalsis and propulsion of content in guinea-pig distal colon? Neuroscience, 240, 325-335.en
dc.descriptionThis article appeared in a journal published by Elsevier Ltd. Under Elsevier's copyright, mandated authors are not permitted to make work available in an institutional repository.en
dc.description.abstractRecent studies have shown genetic deletion of the gene that synthesizes 5-HT in enteric neurons (tryptophan hydroxylase-2, Tph-2) leads to a reduction in intestinal transit. However, deletion of the Tph-2 gene also leads to major developmental changes in enteric ganglia, which could also explain changes in intestinal transit. We sought to investigate this further by acutely depleting serotonin from enteric neurons over a 24-h period, without the confounding influences induced by genetic manipulation. Guinea-pigs were injected with reserpine 24 h prior to euthanasia. Video-imaging and spatio-temporal mapping was used to record peristalsis evoked by natural fecal pellets, or slow infusion of intraluminal fluid. Immunohistochemical staining for 5-HT was used to detect the presence of serotonin in the myenteric plexus. It was found that endogenous 5-HT was always detected in myenteric ganglia of control animals, but never in guinea-pigs treated with reserpine. Interestingly, peristalsis was still reliably evoked by either intraluminal fluid, or fecal pellets in reserpine-treated animals that also had their entire mucosa and submucosal plexus removed. In these 5-HT depleted animals, there was no change in the frequency of peristalsis or force generated during peristalsis. In control animals, or reserpine treated animals, high concentrations (up to 10 μM) of ondansetron and SDZ-205-557, or granisetron and SDZ-205-557 had no effect on peristalsis. In summary, acute depletion of serotonin from enteric nerves does not prevent distension-evoked peristalsis, nor propulsion of luminal content. Also, we found no evidence that 5-HT3 and 5-HT4 receptor activation is required for peristalsis, or propulsion of contents to occur. Taken together, we suggest that the intrinsic mechanisms that generate peristalsis and entrain propagation along the isolated guinea-pig distal colon are independent of 5-HT in enteric neurons or the mucosa, and do not require the activation of 5-HT3 or 5-HT4 receptors.en
dc.description.sponsorshipAustralian National Health & Medical Research Councilen
dc.rightsCopyright 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
dc.subjectEnteric nervous system
dc.subjectMyenteric plexus
dc.subjectDrug research
dc.titleIs serotonin in enteric nerves required for distension-evoked peristalsis and propulsion of content in guinea-pig distal colon?en_US
dc.rights.holderElsevier Ltd.
local.contributor.authorOrcidLookupBrookes, Simon Jonathan:

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