Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine
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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.
I: Neurogastroenterology and Motility, Bind 35, Nr. 8, e14589, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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