Volume 129, Issue 5, Pages 1533-1543 (November 2005) Corticotropin-Releasing Hormone Receptor 1 Antagonist Blocks Brain–Gut Activation Induced by Colonic Distention in Rats  Kumi Saito, Toshiyuki Kasai, Yohko Nagura, Hitomi Ito, Motoyori Kanazawa, Shin Fukudo  Gastroenterology  Volume 129, Issue 5, Pages 1533-1543 (November 2005) DOI: 10.1053/j.gastro.2005.07.053 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 Structure of JTC-017. Gastroenterology 2005 129, 1533-1543DOI: (10.1053/j.gastro.2005.07.053) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 Experimental protocol. (A) Effects of α-helical CRH or (B) JTC-017 on colorectal distention–induced hippocampal noradrenaline release and frequency of abdominal contractions. (C) Effects of JTC-017 on acute or chronic (D) colorectal distention–induced anxiety-related behavior and stress-induced changes in colonic motility. α-h CRH, α-helical CRH; ——, free moving; –––, restraint; gray box with CRD, colorectal distention (80 mm Hg); striped box, EPM. Gastroenterology 2005 129, 1533-1543DOI: (10.1053/j.gastro.2005.07.053) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 Experimental protocol. (A) Effects of α-helical CRH or (B) JTC-017 on colorectal distention–induced hippocampal noradrenaline release and frequency of abdominal contractions. (C) Effects of JTC-017 on acute or chronic (D) colorectal distention–induced anxiety-related behavior and stress-induced changes in colonic motility. α-h CRH, α-helical CRH; ——, free moving; –––, restraint; gray box with CRD, colorectal distention (80 mm Hg); striped box, EPM. Gastroenterology 2005 129, 1533-1543DOI: (10.1053/j.gastro.2005.07.053) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 3 Effects of α-helical CRH on colorectal distention–induced hippocampal noradrenaline release and frequency of abdominal contractions. (A) Colorectal distention–induced hippocampal noradrenaline release and (B) abdominal contractions. Data are expressed as the mean ± SE (n = 6). *P < .05; **P < .01 (vehicle + distention vs α-helical CRH + distention, α-helical CRH + free moving, or vehicle + free moving). Gastroenterology 2005 129, 1533-1543DOI: (10.1053/j.gastro.2005.07.053) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 4 Effect of JTC-017 on colorectal distention–induced hippocampal noradrenaline release and frequency of abdominal contractions. (A) Colorectal distention–induced hippocampal noradrenaline release and (B) abdominal contractions. Data are expressed as the mean ± SE (5 rats per group). *P < .05; **P < .01 (vehicle + distention vs JTC-017 + distention). Gastroenterology 2005 129, 1533-1543DOI: (10.1053/j.gastro.2005.07.053) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 5 Effect of JTC-017 on acute or chronic colorectal distention–induced anxiety-related behavior and stress-induced changes in colonic motility. (A) Acute colorectal distention–induced percentage of time spent in the open arms of the EPM and (B) fecal pellet output. (C) Chronic colorectal distention–induced percentage of time spent in the open arms of the EPM and (D) fecal pellet output. Data are expressed as the mean ± SE (5–6 rats per group). *P < .05 (vehicle + distention vs JTC-017 + distention and control). Gastroenterology 2005 129, 1533-1543DOI: (10.1053/j.gastro.2005.07.053) Copyright © 2005 American Gastroenterological Association Terms and Conditions