1. Expression of functional neurokinin-1 receptors in regenerative glands during gastric wound healing in rodents 
Adrian Schmassmann, Bea Waser, Beatrice Flogerzi, Jean Claude Reubi 
Gastroenterology 
Volume 126, Issue 3, Pages (March 2004)
DOI: /j.gastro

2. Figure 1
Overexpression of SP binding sites in the repair zone in the gastric corpus (A-C) and antrum (D-F) of rats and in the gastric corpus (G-M) of mice. The ulcer crater is surrounded on both sides by an adjacent repair zone of regenerative mucosa followed by the normal oxyntic mucosa (bar = 1 mm in all figures). (A-C) Rat gastric corpus 10 days after ulcer induction. (A) H&E. (B) Autoradiogram showing total binding of 125I-HBSP in the repair zone on both sides of the ulcer crater (arrowheads); m.p., muscularis propria. (C) Autoradiogram showing nonspecific binding (in the presence of SP 1 μmol/L). (D-F) Rat antrum 8 days after ulcer induction. (D) H&E. (E) Autoradiogram shows total binding of 125I-HBSP in the repair zone on both sides (arrowheads). (F) Autoradiogram showing nonspecific binding (in the presence of SP 1 μmol/L). (G-M) Mouse gastric corpus 8 days after ulcer induction. (G-I) Section in the middle of the ulcer crater; the ulcer crater is surrounded by an adjacent repair zone of regenerative mucosa followed by the normal oxyntic mucosa. (K-M) Section in the repair zone; regenerative glands are seen followed by the normal oxyntic mucosa. (G and K) H&E. (H and L) Autoradiograms showing total binding of 125I-HBSP in the repair zone (arrowheads). (I and M) Autoradiograms showing nonspecific binding (in the presence of SP 1 μmol/L).
Gastroenterology  , DOI: ( /j.gastro )

3. Figure 2
Time sequence of expression of NK1Rs (disintegrations per minute/mg tissue) and BrdU-labeled cells (%) in the regenerative mucosal margin during wound healing in the rat gastric corpus between days 1 and 84. NK1Rs were strongly expressed between days 3 and 15, with a peak on day 8. The percentage of BrdU-labeled cells was strongly increased between days 3 and 8. In parallel to wound closure, which occurred between days 15 and 22, the density of NK1Rs and the percentage of BrdU-labeled cells decreased rapidly. Data are expressed as mean ± SEM. ∗P < 0.02 vs. data on day 84.
Gastroenterology  , DOI: ( /j.gastro )

4. Figure 3
Displacement experiment of 125I-HBSP for the NK1R in the repair zone of rats on day 5. Tissue sections were incubated with 125I-HBSP and increasing concentrations of unlabeled SP, the NK1R-selective agonist [Sar9, Met(O2)11]-SP, the NK2R-selective agonist [Nle10]-neurokinin A(4–10), and the NK3R-selective agonist senktide. Unlabeled SP and the NK1R-selective agonist [Sar9, Met(O2)11]-SP displaced the ligand with high affinity. In contrast, the NK2R-selective agonist [Nle10]-neurokinin A(4–10) and the NK3R-selective agonist senktide displaced the ligand with low affinity only.
Gastroenterology  , DOI: ( /j.gastro )

5. Figure 4
Right ulcer margin adjacent to the ulcer crater of rats 8 and 15 days after ulcer induction. Strong immunoreactivity for the NK1R was detected on the cell membrane of regenerative epithelial glands in the gastric corpus adjacent to the ulcer crater both on day 8 (A-C) and on day 15 (D-F). NK1Rs are stained brown in A-F and red in G. Strong NK1R expression was predominantly found in the basal part of the regenerative glands close to the ulcer crater. (A, B, D, and E) Repair tissue at lower magnification (bar = 0.1 mm). (C and F) Further details at higher magnifications (bar = 0.01 mm). (G) Double staining for NK1Rs and BrdU in the repair tissue on day 8 (bar = 0.01 mm). BrdU-labeled cells show brown nuclei (arrows), and NK1Rs show red cell membranes (arrowheads). Although glands with many NK1R-positive cells also show several BrdU-labeled cells within the same gland, BrdU-labeled nuclei are rarely found in NK1R-positive cells. Within each regenerative gland, NK1R immunoreactivity showed a relevant variation between neighboring cells.
Gastroenterology  , DOI: ( /j.gastro )

6. Figure 5
Ulcer area in wild-type and COX-2−/− mice on day 8. Placebo-treated wild-type mice (group 1) showed rapid wound healing with complete re-epithelialization between days 8 and 15. In contrast, wound healing in COX-2−/− mice (group 3) was substantially impaired, as shown by the significantly larger ulcer size on day 8. Compared with placebo-treated animals, the NK1R antagonist NKP608 showed a delay in wound healing in both wild-type mice (group 2) and COX-2−/− mice (group 4). Note that NKP608 did not increase the size of the ulcer, but only delayed the speed of wound healing to such an extent that a larger ulcer is seen on day 8 compared with placebo. Data are expressed as mean ± SEM. ∗P < 0.01 (group 1 vs. 2); ∗∗P < (group 1 vs. 3); ∗∗∗P < 0.05 (group 3 vs. 4). Pl., placebo.
Gastroenterology  , DOI: ( /j.gastro )

7. Figure 6
Left mucosal ulcer margin adjacent to the ulcer crater of mice on day 8. Ki-67-labeled regenerative epithelia (showing dark brown-labeled nuclei) are found in the basal part of the regenerative glands. (A) In placebo-treated wild-type mice (group 1), the mucosal ulcer margin is well developed and long, showing many Ki-67-labeled regenerative epithelial cells. (B) In wild-type mice treated with the NK1R antagonist NKP608 (group 2), the mucosal ulcer margin is shorter and the number of Ki-67-labeled epithelial cells in regenerative glands is decreased compared with placebo-treated wild-type mice (group 1). (C) In COX-2−/− mice treated with NKP608 (group 4), the mucosal ulcer margin is even shorter, and the number of Ki-67-labeled cells is markedly decreased compared with placebo-treated wild-type mice (group 1). Furthermore, the granulation tissue is thick and immature (bar = 0.2 mm).
Gastroenterology  , DOI: ( /j.gastro )