Download presentation
Presentation is loading. Please wait.
Published byŌΣίμων Μαυρίδης Modified over 6 years ago
1
Peripheral and Central P2X3 Receptor Contributions to Colon Mechanosensitivity and Hypersensitivity in the Mouse Masamichi Shinoda, Bin Feng, G.F. Gebhart Gastroenterology Volume 137, Issue 6, Pages (December 2009) DOI: /j.gastro Copyright © 2009 AGA Institute Terms and Conditions
2
Figure 1 (A) Treatment and testing protocol. (B) Baseline (day 4) responses to colon distension are significantly less in P2X3+/− (heterozygous) and P2X3−/− (homozygous) null mice relative to P2X3 wild-type mice (F2,200 = 12.82; *P < .001 compared with P2X3 wild-type mice). Data are expressed as percentage (mean ± SEM) of the visceromotor response to colon distension on the day of baseline testing (day 4) for each animal and normalized to the response to 60 mm Hg distension (100%) to generate stimulus-response functions. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2009 AGA Institute Terms and Conditions
3
Figure 2 (A) Responses to colon distension in P2X3 wild-type mice before (baseline) and after intracolonic (ic) treatment with saline or (B) zymosan (F3,84 = 12.16; *P < .01 on days 7, 10, and 14 compared with baseline). (C) Responses to colon distension in P2X3+/− mice before (baseline) and after intracolonic (ic) treatment with saline or (D) zymosan (F3,72 = 14.86; P < .01 on days 7, 10, and 14 compared with baseline). (E) Responses to colon distension in P2X3−/− mice before and after intracolonic (ic) treatment with saline or (F) zymosan. Colon hypersensitivity did not develop in zymosan-treated P2X3−/− mice. Data are expressed as percentage (mean ± SEM) of the visceromotor response to colon distension on the day of baseline testing (day 4) for each animal and normalized to the response to 60 mm Hg distension (100%) to generate stimulus-response functions. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2009 AGA Institute Terms and Conditions
4
Figure 3 (A) Representative histology of mouse colons from saline- and zymosan-treated mice 7, 10, and 14 days after surgical implantation of EMG electrodes. An example of TNBS-produced colon inflammation (2 days after intracolonic instillation of TNBS) is given for comparison. (B) ATP (nmol/L) released into the lumen of the colon during distension (15, 30, 45, and 60 mm Hg; 10 seconds) in P2X3 wild-type and P2X3−/− mice after intracolonic treatment with saline or zymosan (left) or TNBS (right; note different vertical scales). ATP release from TNBS-treated P2X3 wild-type mice was significantly greater than from zymosan-treated P2X3 wild-type mice (F3,20 = 6.86; P < .005). Data are expressed as mean ± SEM; n = 6/group. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2009 AGA Institute Terms and Conditions
5
Figure 4 Representative examples of responses of 2 muscular afferents to circumferential stretch before (pre) and 2 minutes after (post) application of an inflammatory soup (IS). Responses of fibers from wild-type (A) and P2X3−/− (B) mice are shown. Bottom: the circumferential stretch stimulus (5 mN/s force) was applied to the longitudinal edge of the colon preparation. The forces generated translate to intralumenal pressures between 0 and 45 mm Hg. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2009 AGA Institute Terms and Conditions
6
Figure 5 Responses of muscular (A) and muscular-mucosal (B) afferents to ramped circumferential stretch in wild-type and P2X3−/− mice. Responses to stretch (converted to corresponding pressures) are presented as total number of action potentials in successive bins of 15 mm Hg (see Figure 4). There were no significant differences in baseline responses of either fiber type between wild-type and P2X3−/− mice. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2009 AGA Institute Terms and Conditions
7
Figure 6 Responses of muscular (A and C) and muscular-mucosal (B and D) afferents to ramped circumferential stretch in wild-type and P2X3−/− mice before and after application of inflammatory soup (IS) to their receptive endings. Responses to circumferential stretch of both muscular and muscular-mucosal fiber types (presented as in Figure 5) in wild-type mice (A and B) were sensitized by application of IS (A: F1,18 = 10.18; B: F1,33 = 7.71; P < .01 for both), whereas only muscular-mucosal afferents (D) were sensitized in P2X3−/− mice (F1,24 = 17.91; P < .001). Gastroenterology , DOI: ( /j.gastro ) Copyright © 2009 AGA Institute Terms and Conditions
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.