Endogenous PYY and NPY mediate tonic Y₁- and Y₂-mediated absorption in human and mouse colon
2008
Cox, Helen M.
Objective: To establish the functional significance of endogenous peptide YY (PYY) and neuropeptide Y (NPY) as mediators of Y₁ and Y₂ absorptive tone in colonic mucosa. Methods: Functional studies utilized descending colon from adult mice (wild type [WT] and peptide nulls) and ex vivo human colonic tissue (from patients undergoing bowel resections) measuring changes in basal ion transport. Peak increases in ion transport to Y₁ or Y₂ antagonists (BIBO3304 300 nM; BIIE0246 1 μM) were pooled (mean ± SEM) and compared using Student's unpaired t test (P <= 0.05); some tissues received tetrodotoxin (TTX; 100 nM). PYY-positive L-cell numbers and NPY innervation were also compared. Results: Y₁ and Y₂ tones were present in human and WT mouse colon mucosa and only the latter was TTX sensitive. Y₁ tone was unchanged in NPY⁻/⁻ but was ~90% inhibited in PYY⁻/⁻ and abolished in PYYNPY⁻/⁻ colon mucosa. Y₂ tone was reduced ~50% in NPY⁻/⁻ and PYY⁻/⁻ tissues and was absent from PYYNPY⁻/⁻ colon. Residual Y₂ and Y₁ tones present in PYY⁻/⁻ mucosa were abolished by TTX. PYY ablation had no apparent effect on NPY innervation and PYY-positive cells were observed at the same frequency in NPY⁻/⁻ (56.7 ± 6.8 cells/section) and WT (55.0 ± 4.6 cells/section) colons. Double knockouts lacked PYY and NPY expression, but endocrine cells and enteric nerves were present with similar frequencies to those of WT mice. Conclusion: Endogenous PYY mediates Y₁ absorptive tone that is epithelial in origin, whereas Y₂ tone is a combination of PYY and NPY mediation.
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