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Updated: Jul 29, 2026
In vitro Functional Characterization of Mouse Colorectal Afferent Endings
Published on: January 21, 2015
Multiple Y receptors mediate pancreatic polypeptide responses in mouse colon mucosa
H M Cox1, E L Pollock, I R Tough
1Centre for Neuroscience, King's College London, GKT School of Biomedical Sciences, Guy's Campus, SE1 9RT, London, United Kingdom. helen.m.cox@kcl.ac.uk
Abstract:
A functional study has been performed to characterise the Y receptors responsible for NPY, PYY and PP-stimulated responses in mouse colonic mucosal preparations. Electrogenic ion secretion was stimulated with VIP following which NPY, PYY and PP analogues were, to varying degrees, inhibitory. PYY(3-36), hPP, Gln(23)hPP and rPP were effective but less potent than full length PYY, NPY or their Pro(34)-substituted analogues, while the Y(5) agonist Ala(31), Aib(32)hNPY was the least active peptide tested. The Y(1) antagonists, BIBP3226 and BIBO3304 virtually abolished Pro(34)PYY and PYY responses while PYY(3-36) responses were selectively inhibited by the Y(2) antagonist, BIIE0246. A combination of BIBO3304 and BIIE0246 also partially attenuated hPP responses, leaving residual effects that were most probably Y(4)-mediated. Thus we conclude that Y(1), Y(2) and Y(4) receptors attenuate ion secretion in mouse colon.
Insights
Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) receptors in mouse colon regulate ion secretion. Y(1), Y(2), and Y(4) receptors were found to inhibit this process, impacting gastrointestinal function.
Area of Science:
- Gastroenterology
- Neuroendocrinology
- Molecular Pharmacology
Background:
- Neuropeptide Y (NPY) family peptides, including PYY and PP, play roles in regulating gastrointestinal functions.
- Y receptors are implicated in various physiological processes, but their specific roles in colonic ion secretion require detailed characterization.
Purpose of the Study:
- To functionally characterize the Y receptors mediating NPY, PYY, and PP actions in mouse colonic mucosal preparations.
- To determine the specific Y receptor subtypes involved in regulating electrogenic ion secretion in the colon.
Main Methods:
- Functional assays using mouse colonic mucosal preparations to measure electrogenic ion secretion.
- Stimulation with vasoactive intestinal peptide (VIP) followed by administration of NPY, PYY, and PP analogues.
- Selective blockade of Y receptor subtypes using specific antagonists (BIBP3226, BIBO3304 for Y1; BIIE0246 for Y2).
Main Results:
- NPY, PYY, and PP analogues exhibited inhibitory effects on VIP-stimulated ion secretion to varying degrees.
- PYY(3-36), hPP, Gln(23)hPP, and rPP were less potent than full-length PYY or NPY analogues.
- Y(1) antagonists abolished Pro(34)PYY and PYY responses, while the Y(2) antagonist selectively inhibited PYY(3-36) responses.
- Combined Y(1) and Y(2) antagonism partially inhibited hPP responses, suggesting a role for Y(4) receptors.
Conclusions:
- Y(1), Y(2), and Y(4) receptors are expressed and functionally active in the mouse colon.
- These receptors play a significant role in attenuating electrogenic ion secretion in the colonic mucosa.
- Understanding these receptor functions provides insights into the neuro-immune regulation of intestinal fluid balance.
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