Effect of otilonium bromide and ibodutant on the internalization of the NK2 receptor in human colon

Background The present aim was to study the modulation of NK₂ receptor internalization by two compounds, the spasmolytic otilonium bromide (OB) endowed with NK₂ receptor antagonistic properties and the selective NK₂ receptor antagonist ibodutant. Methods Full‐thickness human colonic segments were incubated in the presence of OB (0.1–10 μmol L^?1) or ibodutant (0.001–0.1 μmol L^?1), with or without the NK₂ receptor selective agonist βAla⁸]NKA(4–10) and then fixed in 4% paraformaldehyde. Cryosections were processed for NK₂ receptor immunohistochemical revelation. Quantitative analysis evaluated the number of the smooth muscle cells that had internalized the NK₂ receptor. Key Results Immuno‐histochemistry revealed that in basal condition, the NK₂ receptor was internalized in about 23% of total smooth muscle cells. The exposure to the selective NK₂ receptor agonist induced internalization of the receptor in more than 77% of the cells. Previous exposure to both OB or ibodutant, either alone or in the presence of the agonist, concentration‐dependently reduced the number of the cells with the internalized receptor. Conclusions & Inferences Both OB and ibodutant antagonize the internalization of the NK₂ receptor in the human colon. As NK₂ receptors are the predominant receptor mediating spasmogenic activity of tachykinins on enteric smooth muscle, we hypothesize that the antagonistic activity found for both OB and ibodutant should play a specific therapeutic role in gut diseases characterized by hypermotility.