Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine

Research output: Contribution to journal › Journal article › Research › peer-review

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Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine. / Tough, Iain R.; Lund, Mari L.; Patel, Bhavik A.; Schwartz, Thue W.; Cox, Helen M.

In: Neurogastroenterology and Motility, Vol. 35, No. 8, e14589, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Tough, IR, Lund, ML, Patel, BA, Schwartz, TW & Cox, HM 2023, 'Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine', Neurogastroenterology and Motility, vol. 35, no. 8, e14589. https://doi.org/10.1111/nmo.14589

APA

Tough, I. R., Lund, M. L., Patel, B. A., Schwartz, T. W., & Cox, H. M. (2023). Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine. Neurogastroenterology and Motility, 35(8), [e14589]. https://doi.org/10.1111/nmo.14589

Vancouver

Tough IR, Lund ML, Patel BA, Schwartz TW, Cox HM. Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine. Neurogastroenterology and Motility. 2023;35(8). e14589. https://doi.org/10.1111/nmo.14589

Author

Tough, Iain R. ; Lund, Mari L. ; Patel, Bhavik A. ; Schwartz, Thue W. ; Cox, Helen M. / Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine. In: Neurogastroenterology and Motility. 2023 ; Vol. 35, No. 8.

Bibtex

@article{9415ac26638d4b4bbf1999d0bc40bd6c,
title = "Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine",
abstract = "Background: Enterochromaffin (EC) cell-derived 5-hydroxytryptamine (5-HT) is a mediator of toxin-induced reflexes, initiating emesis via vagal and central 5-HT3 receptors. The amine is also involved in gastrointestinal (GI) reflexes that are prosecretory and promotile, and recently 5-HT's roles in chemosensation in the distal bowel have been described. We set out to establish the efficacy of 5-HT signaling, local 5-HT levels and pharmacology in discrete regions of the mouse small and large intestine. We also investigated the inter-relationships between incretin hormones, glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) and endogenous 5-HT in mucosal and motility assays. Methods: Adult mouse GI mucosae were mounted in Ussing chambers and area-specific studies were performed to establish the 5-HT3 and 5-HT4 pharmacology, the sidedness of responses, and the inter-relationships between incretins and endogenous 5-HT. Natural fecal pellet transit in vitro and full-length GI transit in vivo were also measured. Key Results: We observed the greatest level of tonic and exogenous 5-HT-induced ion transport and highest levels of 5-HT in ascending colon mucosa. Here both 5-HT3 and 5-HT4 receptors were involved but elsewhere in the GI tract epithelial basolateral 5-HT4 receptors mediate 5-HT's prosecretory effect. Exendin-4 and GIP induced 5-HT release in the ascending colon, while L cell-derived PYY also contributed to GIP mucosal effects in the descending colon. Both peptides slowed colonic transit. Conclusions & Inferences: We provide functional evidence for paracrine interplay between 5-HT, GLP-1 and GIP, particularly in the colonic mucosal region. Basolateral epithelial 5-HT4 receptors mediated both 5-HT and incretin mucosal responses in healthy colon.",
keywords = "5-hydroxytryptamine, enterochromaffin cells, gastric inhibitory polypeptide, glucagon-like peptide-1, motility, mucosal ion transport",
author = "Tough, {Iain R.} and Lund, {Mari L.} and Patel, {Bhavik A.} and Schwartz, {Thue W.} and Cox, {Helen M.}",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.",
year = "2023",
doi = "10.1111/nmo.14589",
language = "English",
volume = "35",
journal = "Neurogastroenterology and Motility Online",
issn = "1365-2982",
publisher = "Wiley-Blackwell",
number = "8",

}

RIS

TY - JOUR

T1 - Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine

AU - Tough, Iain R.

AU - Lund, Mari L.

AU - Patel, Bhavik A.

AU - Schwartz, Thue W.

AU - Cox, Helen M.

N1 - Publisher Copyright: © 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

PY - 2023

Y1 - 2023

N2 - Background: Enterochromaffin (EC) cell-derived 5-hydroxytryptamine (5-HT) is a mediator of toxin-induced reflexes, initiating emesis via vagal and central 5-HT3 receptors. The amine is also involved in gastrointestinal (GI) reflexes that are prosecretory and promotile, and recently 5-HT's roles in chemosensation in the distal bowel have been described. We set out to establish the efficacy of 5-HT signaling, local 5-HT levels and pharmacology in discrete regions of the mouse small and large intestine. We also investigated the inter-relationships between incretin hormones, glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) and endogenous 5-HT in mucosal and motility assays. Methods: Adult mouse GI mucosae were mounted in Ussing chambers and area-specific studies were performed to establish the 5-HT3 and 5-HT4 pharmacology, the sidedness of responses, and the inter-relationships between incretins and endogenous 5-HT. Natural fecal pellet transit in vitro and full-length GI transit in vivo were also measured. Key Results: We observed the greatest level of tonic and exogenous 5-HT-induced ion transport and highest levels of 5-HT in ascending colon mucosa. Here both 5-HT3 and 5-HT4 receptors were involved but elsewhere in the GI tract epithelial basolateral 5-HT4 receptors mediate 5-HT's prosecretory effect. Exendin-4 and GIP induced 5-HT release in the ascending colon, while L cell-derived PYY also contributed to GIP mucosal effects in the descending colon. Both peptides slowed colonic transit. Conclusions & Inferences: We provide functional evidence for paracrine interplay between 5-HT, GLP-1 and GIP, particularly in the colonic mucosal region. Basolateral epithelial 5-HT4 receptors mediated both 5-HT and incretin mucosal responses in healthy colon.

AB - Background: Enterochromaffin (EC) cell-derived 5-hydroxytryptamine (5-HT) is a mediator of toxin-induced reflexes, initiating emesis via vagal and central 5-HT3 receptors. The amine is also involved in gastrointestinal (GI) reflexes that are prosecretory and promotile, and recently 5-HT's roles in chemosensation in the distal bowel have been described. We set out to establish the efficacy of 5-HT signaling, local 5-HT levels and pharmacology in discrete regions of the mouse small and large intestine. We also investigated the inter-relationships between incretin hormones, glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) and endogenous 5-HT in mucosal and motility assays. Methods: Adult mouse GI mucosae were mounted in Ussing chambers and area-specific studies were performed to establish the 5-HT3 and 5-HT4 pharmacology, the sidedness of responses, and the inter-relationships between incretins and endogenous 5-HT. Natural fecal pellet transit in vitro and full-length GI transit in vivo were also measured. Key Results: We observed the greatest level of tonic and exogenous 5-HT-induced ion transport and highest levels of 5-HT in ascending colon mucosa. Here both 5-HT3 and 5-HT4 receptors were involved but elsewhere in the GI tract epithelial basolateral 5-HT4 receptors mediate 5-HT's prosecretory effect. Exendin-4 and GIP induced 5-HT release in the ascending colon, while L cell-derived PYY also contributed to GIP mucosal effects in the descending colon. Both peptides slowed colonic transit. Conclusions & Inferences: We provide functional evidence for paracrine interplay between 5-HT, GLP-1 and GIP, particularly in the colonic mucosal region. Basolateral epithelial 5-HT4 receptors mediated both 5-HT and incretin mucosal responses in healthy colon.

KW - 5-hydroxytryptamine

KW - enterochromaffin cells

KW - gastric inhibitory polypeptide

KW - glucagon-like peptide-1

KW - motility

KW - mucosal ion transport

U2 - 10.1111/nmo.14589

DO - 10.1111/nmo.14589

M3 - Journal article

C2 - 37010838

AN - SCOPUS:85151458808

VL - 35

JO - Neurogastroenterology and Motility Online

JF - Neurogastroenterology and Motility Online

SN - 1365-2982

IS - 8

M1 - e14589

ER -

ID: 345015322