British journal of pharmacologyApr 5, 2011

Peptide YY and neuropeptide Y differently reduce colon movement and fluid transport through Y1 and Y2 receptors

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 28, 2026

Abstract

Y₁ and Y₂ receptors mediate significant mucosal antisecretory effects, with 90% reduction in Y₁ tone observed in PYY⁻/⁻ mice.

Y₁ receptor activity was primarily epithelial, whereas Y₂ receptor activity was neuronal in both human and mouse colon mucosae.
Y₁ tone was significantly reduced in the absence of PYY, while NPY absence did not affect Y₁ tone.
Y₂ tone was partially reduced in individual peptide knockout tissues and completely abolished in tetrodotoxin-pretreated PYY⁻/⁻ tissue.
Inhibition of colonic transit was associated with Y₁ blockade, while Y₂ antagonism increased colonic transit.
Upper gastrointestinal transit was found to be increased in PYY⁻/⁻ mice, indicating a specific role for PYY in this process.
Y₂ receptor blockade led to a decrease in the frequency of colonic migrating motor complexes in isolated mouse colon.

Simplified

BACKGROUND AND PURPOSE: Peptide YY (PYY) and neuropeptide Y (NPY) activate Y receptors, targets under consideration as treatments for diarrhoea and other intestinal disorders. We investigated the gastrointestinal consequences of selective PYY or NPY ablation on mucosal ion transport, smooth muscle activity and transit using wild-type, single and double peptide knockout mice, comparing mucosal responses with those from human colon.

EXPERIMENTAL APPROACH: Mucosae were pretreated with a Y₁ (BIBO3304) or Y₂ (BIIE0246) receptor antagonist and changes in short-circuit current recorded. Colonic transit and colonic migrating motor complexes (CMMCs) were assessed in vitro and upper gastrointestinal and colonic transit measured in vivo.

KEY RESULTS: Y receptor antagonists revealed tonic Y₁ and Y₂ receptor-mediated antisecretory effects in human and wild-type mouse colon mucosae. In both, Y₁ tone was epithelial while Y₂ tone was neuronal. Y₁ tone was reduced 90% in PYY⁻/⁻ mucosa but unchanged in NPY⁻/⁻ tissue. Y₂ tone was partially reduced in NPY⁻/⁻ or PYY⁻/⁻ mucosae and abolished in tetrodotoxin-pretreated PYY⁻/⁻ tissue. Y₁ and Y₂ tone were absent in NPYPYY⁻/⁻ tissue. Colonic transit was inhibited by Y₁ blockade and increased by Y₂ antagonism indicating tonic Y₁ excitation and Y₂ inhibition respectively. Upper GI transit was increased in PYY⁻/⁻ mice only. Y₂ blockade reduced CMMC frequency in isolated mouse colon.

CONCLUSIONS AND IMPLICATIONS: Endogenous PYY and NPY induced significant mucosal antisecretory tone mediated by Y₁ and Y₂ receptors, via similar mechanisms in human and mouse colon mucosa. Both peptides contributed to tonic Y₂-receptor-mediated inhibition of colonic transit in vitro but only PYY attenuated upper GI transit.

Full Text

Full text is available at the source.

View Full Text ↗

Peptide YY and neuropeptide Y differently reduce colon movement and fluid transport through Y1 and Y2 receptors

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief