title: Is serotonin in enteric nerves required for distension-evoked peristalsis and propulsion of content in guinea-pig distal colon?
abstract: Recent 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 24h 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.
authors.affiliation: Discipline of Human Physiology & Center for Neuroscience, Flinders Medical Center, South Australia, Australia.
authors.forename: T C
authors.initials: TC
authors.lastname: Sia
authors.forename: N
authors.initials: N
authors.lastname: Flack
authors.forename: L
authors.initials: L
authors.lastname: Robinson
authors.forename: M
authors.initials: M
authors.lastname: Kyloh
authors.forename: S J
authors.initials: SJ
authors.lastname: Nicholas
authors.forename: S J
authors.initials: SJ
authors.lastname: Brookes
authors.forename: D A
authors.initials: DA
authors.lastname: Wattchow
authors.forename: P
authors.initials: P
authors.lastname: Dinning
authors.forename: J
authors.initials: J
authors.lastname: Oliver
authors.forename: N J
authors.initials: NJ
authors.lastname: Spencer
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000294:innervation* / Q000502:physiology; D017615:Enteric Nervous System / Q000187:drug effects / Q000378:metabolism*; D005071:Evoked Potentials / Q000502:physiology*; D005243:Feces; D006168:Guinea Pigs; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism; D010528:Peristalsis / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects / Q000379:methods; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014741:Video Recording; D062366:para-Aminobenzoates / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D012702:Serotonin Antagonists; D062366:para-Aminobenzoates; C072790:2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester; D012701:Serotonin; D012110:Reserpine