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Endogenous PYY and NPY mediate tonic Y1- and Y2-mediated absorption in human and mouse colon.

Cox HM - Nutrition (2008)

Bottom Line: PYY-positive L-cell numbers and NPY innervation were also compared.Y(2) tone was reduced approximately 50% in NPY(-/-) and PYY(-/-) tissues and was absent from PYYNPY(-/-) colon.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.

View Article: PubMed Central - PubMed

Affiliation: King's College London, Wolfson Centre for Age-Related Diseases, Guy's Campus, London, United Kingdom. helen.cox@kcl.ac.uk

ABSTRACT

Objective: To establish the functional significance of endogenous peptide YY (PYY) and neuropeptide Y (NPY) as mediators of Y(1) and Y(2) absorptive tone in colonic mucosa.

Methods: Functional studies utilized descending colon from adult mice (wild type [WT] and peptide s) and ex vivo human colonic tissue (from patients undergoing bowel resections) measuring changes in basal ion transport. Peak increases in ion transport to Y(1) or Y(2) antagonists (BIBO3304 300 nM; BIIE0246 1 microM) were pooled (mean +/- SEM) and compared using Student's unpaired t test (P

Results: Y(1) and Y(2) tones were present in human and WT mouse colon mucosa and only the latter was TTX sensitive. Y(1) tone was unchanged in NPY(-/-) but was approximately 90% inhibited in PYY(-/-) and abolished in PYYNPY(-/-) colon mucosa. Y(2) tone was reduced approximately 50% in NPY(-/-) and PYY(-/-) tissues and was absent from PYYNPY(-/-) colon. Residual Y(2) and Y(1) 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 Y(1) absorptive tone that is epithelial in origin, whereas Y(2) tone is a combination of PYY and NPY mediation.

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Effects of individual NPY or PYY ablation (NPY−/−, PYY−/−) and double knockout (NPYPYY−/−) on Y1 and Y2 tone in mouse colon mucosa. (A) WT Y1 tone was similar to that of NPY−/− with or without TTX but was absent from NPYPYY−/− tissues (**P ≤ 0.01). (B) Y2 tone was partially reduced in NPY−/− tissue with or without TTX (not significantly) and abolished in NPYPYY−/− preparations (*P ≤ 0.05). (C) Y1 tone was reduced in PYY−/− colon (***P ≤ 0.001) and residual Y1 tone was abolished by neuronal blockade with TTX. (D) Y2 tone was partially inhibited in PYY−/− mucosae (*P ≤ 0.05) and abolished by TTX. Bars represent mean ± SEM from 3–7 observations. ΔIsc, change in short-circuit current; NPY−/−, neuropeptide Y single knockout; NPYPYY−/−, peptide YY/neuropeptide Y double knockout; PYY−/−, peptide YY single knockout; TTX, tetrodotoxin; WT, wild-type.
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fig2: Effects of individual NPY or PYY ablation (NPY−/−, PYY−/−) and double knockout (NPYPYY−/−) on Y1 and Y2 tone in mouse colon mucosa. (A) WT Y1 tone was similar to that of NPY−/− with or without TTX but was absent from NPYPYY−/− tissues (**P ≤ 0.01). (B) Y2 tone was partially reduced in NPY−/− tissue with or without TTX (not significantly) and abolished in NPYPYY−/− preparations (*P ≤ 0.05). (C) Y1 tone was reduced in PYY−/− colon (***P ≤ 0.001) and residual Y1 tone was abolished by neuronal blockade with TTX. (D) Y2 tone was partially inhibited in PYY−/− mucosae (*P ≤ 0.05) and abolished by TTX. Bars represent mean ± SEM from 3–7 observations. ΔIsc, change in short-circuit current; NPY−/−, neuropeptide Y single knockout; NPYPYY−/−, peptide YY/neuropeptide Y double knockout; PYY−/−, peptide YY single knockout; TTX, tetrodotoxin; WT, wild-type.

Mentions: To establish the relative contributions of endogenous NPY and PYY toward each Y-receptor–mediated tone, we monitored the effects of Y1 or Y2 antagonists in colon mucosa from single knockout mice (NPY−/− or PYY−/−) and the double- mice (NPYPYY−/−). Comparison of the maximal increases in Isc 15 min after antagonist additions in WT versus mucosa showed that NPY−/− colon exhibited normal Y1 tone (that was not TTX sensitive; Fig. 2A), whereas Y2 tone was partially (but not significantly) reduced by NPY ablation (Fig. 2B). TTX pretreatment of NPY−/− tissue did not further inhibit Y1 or Y2 residual tone (Fig. 2A,B). In marked contrast, PYY−/− mucosa was markedly less sensitive than WT colon to Y1 (Fig. 2C) and Y2 (Fig. 2D) antagonism and blocking neuronal activity in this tissue abolished these residual increases in Isc. NPYPYY−/− tissues were insensitive to both Y antagonists (Fig. 2A,B).


Endogenous PYY and NPY mediate tonic Y1- and Y2-mediated absorption in human and mouse colon.

Cox HM - Nutrition (2008)

Effects of individual NPY or PYY ablation (NPY−/−, PYY−/−) and double knockout (NPYPYY−/−) on Y1 and Y2 tone in mouse colon mucosa. (A) WT Y1 tone was similar to that of NPY−/− with or without TTX but was absent from NPYPYY−/− tissues (**P ≤ 0.01). (B) Y2 tone was partially reduced in NPY−/− tissue with or without TTX (not significantly) and abolished in NPYPYY−/− preparations (*P ≤ 0.05). (C) Y1 tone was reduced in PYY−/− colon (***P ≤ 0.001) and residual Y1 tone was abolished by neuronal blockade with TTX. (D) Y2 tone was partially inhibited in PYY−/− mucosae (*P ≤ 0.05) and abolished by TTX. Bars represent mean ± SEM from 3–7 observations. ΔIsc, change in short-circuit current; NPY−/−, neuropeptide Y single knockout; NPYPYY−/−, peptide YY/neuropeptide Y double knockout; PYY−/−, peptide YY single knockout; TTX, tetrodotoxin; WT, wild-type.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2572019&req=5

fig2: Effects of individual NPY or PYY ablation (NPY−/−, PYY−/−) and double knockout (NPYPYY−/−) on Y1 and Y2 tone in mouse colon mucosa. (A) WT Y1 tone was similar to that of NPY−/− with or without TTX but was absent from NPYPYY−/− tissues (**P ≤ 0.01). (B) Y2 tone was partially reduced in NPY−/− tissue with or without TTX (not significantly) and abolished in NPYPYY−/− preparations (*P ≤ 0.05). (C) Y1 tone was reduced in PYY−/− colon (***P ≤ 0.001) and residual Y1 tone was abolished by neuronal blockade with TTX. (D) Y2 tone was partially inhibited in PYY−/− mucosae (*P ≤ 0.05) and abolished by TTX. Bars represent mean ± SEM from 3–7 observations. ΔIsc, change in short-circuit current; NPY−/−, neuropeptide Y single knockout; NPYPYY−/−, peptide YY/neuropeptide Y double knockout; PYY−/−, peptide YY single knockout; TTX, tetrodotoxin; WT, wild-type.
Mentions: To establish the relative contributions of endogenous NPY and PYY toward each Y-receptor–mediated tone, we monitored the effects of Y1 or Y2 antagonists in colon mucosa from single knockout mice (NPY−/− or PYY−/−) and the double- mice (NPYPYY−/−). Comparison of the maximal increases in Isc 15 min after antagonist additions in WT versus mucosa showed that NPY−/− colon exhibited normal Y1 tone (that was not TTX sensitive; Fig. 2A), whereas Y2 tone was partially (but not significantly) reduced by NPY ablation (Fig. 2B). TTX pretreatment of NPY−/− tissue did not further inhibit Y1 or Y2 residual tone (Fig. 2A,B). In marked contrast, PYY−/− mucosa was markedly less sensitive than WT colon to Y1 (Fig. 2C) and Y2 (Fig. 2D) antagonism and blocking neuronal activity in this tissue abolished these residual increases in Isc. NPYPYY−/− tissues were insensitive to both Y antagonists (Fig. 2A,B).

Bottom Line: PYY-positive L-cell numbers and NPY innervation were also compared.Y(2) tone was reduced approximately 50% in NPY(-/-) and PYY(-/-) tissues and was absent from PYYNPY(-/-) colon.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.

View Article: PubMed Central - PubMed

Affiliation: King's College London, Wolfson Centre for Age-Related Diseases, Guy's Campus, London, United Kingdom. helen.cox@kcl.ac.uk

ABSTRACT

Objective: To establish the functional significance of endogenous peptide YY (PYY) and neuropeptide Y (NPY) as mediators of Y(1) and Y(2) absorptive tone in colonic mucosa.

Methods: Functional studies utilized descending colon from adult mice (wild type [WT] and peptide s) and ex vivo human colonic tissue (from patients undergoing bowel resections) measuring changes in basal ion transport. Peak increases in ion transport to Y(1) or Y(2) antagonists (BIBO3304 300 nM; BIIE0246 1 microM) were pooled (mean +/- SEM) and compared using Student's unpaired t test (P

Results: Y(1) and Y(2) tones were present in human and WT mouse colon mucosa and only the latter was TTX sensitive. Y(1) tone was unchanged in NPY(-/-) but was approximately 90% inhibited in PYY(-/-) and abolished in PYYNPY(-/-) colon mucosa. Y(2) tone was reduced approximately 50% in NPY(-/-) and PYY(-/-) tissues and was absent from PYYNPY(-/-) colon. Residual Y(2) and Y(1) 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 Y(1) absorptive tone that is epithelial in origin, whereas Y(2) tone is a combination of PYY and NPY mediation.

Show MeSH
Related in: MedlinePlus