Endocannabinoids as physiological regulators of colonic propulsion in mice  Luisa Pinto, Angelo A. Izzo, Nicola Mascolo, Francesco Capasso  Gastroenterology  Volume 123, Issue 1, Pages 227-234 (July 2002) DOI: 10.1053/gast.2002.34242 Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 1 Dose-response curves for IP-injected WIN 55,212-2 (0.1–3 mg/kg), ACEA (0.1–3 mg/ kg), anandamide (2.5–20 mg/kg), cannabinol (3.75–30 mg/kg), and JWH-015 (1–10 mg/kg). Each point represents the MET ± SEM of a glass bead inserted into the distal colon of ≥12 mice. Results are expressed as **P < 0.01 and ***P < 0.001 vs. control. Gastroenterology 2002 123, 227-234DOI: (10.1053/gast.2002.34242) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 2 Effects of IP-injected WIN 55,212-2 (1 mg/kg), ACEA (0.3 mg/kg), cannabinol (20 mg/kg), and anandamide (10 mg/kg) on colonic propulsion alone or in mice treated with SR141716A (1 mg/kg). Each point represents the MET ± SEM of a glass bead inserted into the distal colon of ≥12 mice. **P < 0.01 and ***P < 0.001 vs. control. Gastroenterology 2002 123, 227-234DOI: (10.1053/gast.2002.34242) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 3 Effect of SR141716A (0.3–20 mg/kg, IP) and SR144528 (0.3–10 mg/kg, IP) on colonic propulsion mice. Each point represents the MET ± SEM of a glass bead inserted into the distal colon of ≥12 mice.**P < 0.01 vs. control. Gastroenterology 2002 123, 227-234DOI: (10.1053/gast.2002.34242) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 4 Effect of the anandamide transporter inhibitor VDM11 (10 mg/kg IP) on colonic propulsion alone or in mice treated with SR141716A (1 mg/kg IP). Each point represents the MET ± SEM of a glass bead inserted into the distal colon of 10–12 mice. **P < 0.01 vs. control; #P < 0.01 vs. VDM11. Gastroenterology 2002 123, 227-234DOI: (10.1053/gast.2002.34242) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 5 Localization of CB1-R, ChAT, and neuronal NOS immunoreactivities in the murine distal colon. A and B show colocalization of CB1-R and ChAT immunoreactivities, whereas C and D demonstrate no colocalization of CB1-R and NOS immunoreactivities. (A) CB1-R immunoreactivity (detected with rabbit anti-human CB1-R antiserum) in a representative transverse section of murine colon is localized to myenteric neurons (arrow) and fibers (single arrowhead). Immunoreactivity is also present in some submucosal neurons (double arrow). (B) ChAT immunoreactivity is observed in myenteric neurons (arrow) and fibers (single arrowhead), and submucosal neurons (double arrow) that were immunoreactive for CB1-R as seen in A. (C) CB1-R immunoreactivity (detected with goat anti-human CB1-R antiserum) in a representative longitudinal section of murine colon is observed in myenteric neurons (arrow). (D) NOS immunoreactivity is observed in myenteric neurons (arrow) and axonal profiles (arrowheads) that were not immunoreactive for CB1-R as seen in C. Hatched arrows indicate absence of NOS-immunoreactivity on CB1-R-immunoreactive neurons. LM, longitudinal muscle; CM, circular muscle. Bar: A–D = 50 μm. Gastroenterology 2002 123, 227-234DOI: (10.1053/gast.2002.34242) Copyright © 2002 American Gastroenterological Association Terms and Conditions