CoChat
Sign Up
Cited by 144Gastrointestinal motility and disordersCongenital gastrointestinal and neural anomaliesNeuropeptides and Animal Physiology

Important role of mucosal serotonin in colonic propulsion and peristaltic reflexes: in vitro analyses in mice lacking tryptophan hydroxylase 1

Open access
Heredia, Dante J., Gershon, Michael D., Koh, Sang Don, Corrigan, Robert D., Okamoto, Takanubu, Smith, Terence K.·2013·The Journal of Physiology
DOI 10.1113/jphysiol.2013.256230PMC PMC3872763
Open this paper in CoChat — free account

Abstract

Previous studies have indicated that neither neuronal nor mucosal 5-hydroxytryptamine (5-HT) are important for colonic migrating motor complexes (CMMCs) or faecal pellet propulsion. Therefore, tryptophan hydroxylase 1 knockout (TPH1KO) mice were used to examine the role of mucosal 5-HT in generating CMMCs and faecal pellet propulsion, as TPH1 is the regulatory enzyme necessary for the synthesis of 5-HT in enterochromaffin cells in the mucosa. Control mice generated a robust CMMC when the mucosa was mechanically stimulated, which was blocked by ondansetron (5-HT3 antagonist), and could propagate faecal pellets that did not significantly distend the bowel, suggesting that they were propelled by mucosal reflexes in the absence of stretch reflexes. TPH1KO mice exhibited no mucosal reflexes, reduced responses to intraluminal distension and propelled only larger faecal pellets, suggesting that they relied upon stretch reflexes alone. In control mice, CMMCs, which can propel a faecal pellet, propagated in an oral to anal direction, whereas, in TPH1KO mice, they rarely propagated. Both the propagation and amplitude of CMMCs were reduced by ondansetron in control mice, whereas this drug did not affect CMMCs in TPH1KO mice. This suggests that 5-HT release from the mucosa and stretch reflexes are important for normal colonic propulsion. Abstract Although there is general agreement that mucosal 5-hydroxytryptamine (5-HT) can initiate peristaltic reflexes in the colon, recent studies have differed as to whether or not the role of mucosal 5-HT is critical. We therefore tested the hypothesis that the secretion of 5-HT from mucosal enterochromaffin (EC) cells is essential for the manifestation of murine colonic peristaltic reflexes. To do so, we analysed the mechanisms underlying faecal pellet propulsion in isolated colons of mice lacking tryptophan hydroxylase 1 (Tph1−/− mice), which is the rate-limiting enzyme in the biosynthesis of mucosal but not neuronal 5-HT. We used video analysis of faecal pellet propulsion, tension transducers to record colonic migrating motor complexes (CMMCs) and intracellular microelectrodes to record circular muscle activity occurring spontaneously or following intraluminal distension. When compared with control (Tph1+/+) mice, Tph1−/− animals exhibited: (1) an elongated colon; (2) larger faecal pellets; (3) orthograde propulsion followed by retropulsion (not observed in Tph1+/+ colon); (4) slower in vitro propulsion of larger faecal pellets (28% of Tph1+/+); (5) CMMCs that infrequently propagated in an oral to anal direction because of impaired descending inhibition; (6) reduced CMMCs and inhibitory responses to intraluminal balloon distension; (7) an absence of reflex activity in response to mucosal stimulation. In addition, (8) thin pellets that propagated along the control colon failed to do so in Tph1−/− colon; and (9) the 5-HT3 receptor antagonist ondansetron, which reduced CMMCs and blocked their propagation in Tph1+/+ mice, failed to alter CMMCs in Tph1−/− animals. Our observations suggest that mucosal 5-HT is essential for reflexes driven by mucosal stimulation and is also important for normal propagation of CMMCs and propulsion of pellets in the isolated colon.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1113/jphysiol.2013.256230

Cites

76 of 76 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Heredia, D. J., Gershon, M. D., Koh, S. D., Corrigan, R. D., Okamoto, T., & Smith, T. K.
Affiliations
  • University of Nevada, Reno (US)
  • Columbia University (US)
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2013-11-11
Volume
591
Issue
23
Pages
5939-5957
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.2013.256230
PMC
PMC3872763
OpenAlex
W1547288529
Cited by
144
References
76
Citations by year
2026: 3 · 2025: 4 · 2024: 5 · 2023: 10 · 2022: 14 · 2021: 16 · 2020: 11 · 2019: 17 · 2018: 21 · 2017: 8 · 2016: 17 · 2015: 10 · 2014: 8
FWCI
11.02
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ns015547-39, 5p20gm103513-10)
  • National Institute of General Medical Sciences (P20 GM-103513, COBRE 8P20GM103513-09)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK 45713, P01DK041315, R01DK045713, P01DK41315)
  • National Institute of Neurological Disorders and Stroke (R01NS012969, NS12969, R01-NS015547, NS 15547)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
serotonin, colonic peristalsis, tryptophan hydroxylase 1, enterochromaffin cells, stretch reflex, ondansetron, colonic motility
MeSH terms
Animals, Colon, Intestinal Mucosa, Male, Mice, Inbred C57BL, Peristalsis, Reflex, Serotonin, Tryptophan Hydroxylase, Myoelectric Complex, Migrating, Mice, Knockout, Receptors, Serotonin, 5-HT3, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review