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


Prof. M. G. Vannucchi, Department of Anatomy, Histology and Forensic Medicine, University of Florence, V.le Pieraccini, 650139 Firenze, Italy.
Tel: +39 055 4271389; fax: +39 055 4271385;
e-mail: mariagiuliana.vannucchi@unifi.it


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.