title: Repeated otilonium bromide administration prevents neurotransmitter changes in colon of rats underwent to wrap restraint stress.
abstract: Otilonium bromide (OB) is a spasmolytic drug successfully used for the treatment of irritable bowel syndrome (IBS). Its efficacy has been attributed to the block of L- and T-type Ca2+channels and muscarinic and tachykinin receptors in the smooth muscle. Furthermore, in healthy rats, repeated OB administration modified neurotransmitter expression and function suggesting other mechanisms of action. On this basis, we investigated whether repeated OB treatment prevented the functional and neurochemical changes observed in the colon of rats underwent to wrap restrain stress (WRS) a psychosocial stressor considered suitable to reproduce the main IBS signs and symptoms. In control, WRS and OB/WRS rats functional parameters were measured in vivo and morphological investigations were done ex vivo in the colon. The results showed that OB counteracts most of the neurotransmitters changes caused by WRS. In particular, the drug prevents the decrease in SP-, NK1r-, nNOS-, VIP-, and S100β-immunoreactivity (IR) and the increase in CGRP-, and CRF1r-IR. On the contrary, OB does not affect the increase in CRF2r-IR neurons observed in WRS rats and does not interfere with the mild mucosal inflammation due to WRS. Finally, OB per se increases the Mr2 expression in the muscle wall and decreases the number of the myenteric ChAT-IR neurons. Functional findings show a significantly reduction in the number of spontaneous abdominal contraction in OB treated rats. The ability of OB to block L-type Ca2+channels, also expressed by enteric neurons, might represent a possible mechanism through which OB exerts its actions.
authors.affiliation: Department of Experimental and Clinical Medicine, Research Unit of Histology and Embryology, Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Traini
authors.affiliation: Ricerche SpA, Preclinical Development Dept., Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Evangelista
authors.affiliation: Syncrosome, Marseille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Girod
authors.affiliation: Department of Experimental and Clinical Medicine, Research Unit of Histology and Embryology, Florence, Italy.
authors.forename: Maria Simonetta
authors.initials: MS
authors.lastname: Faussone-Pellegrini
authors.affiliation: Department of Experimental and Clinical Medicine, Research Unit of Histology and Embryology, Florence, Italy.
authors.forename: Maria Giuliana
authors.initials: MG
authors.lastname: Vannucchi
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D056885:Interstitial Cells of Cajal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology; D009130:Muscle, Smooth / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D018377:Neurotransmitter Agents; D000644:Quaternary Ammonium Compounds; D043585:Receptor, Muscarinic M2; D018019:Receptors, Corticotropin-Releasing Hormone; D018040:Receptors, Neurokinin-1; C013934:octylonium; D014660:Vasoactive Intestinal Peptide; D000099052:CRF Receptor, Type 1; D019009:Proto-Oncogene Proteins c-kit; D015740:Calcitonin Gene-Related Peptide
keywords: corticotrophin releasing factor receptors; immunohistochemistry; inflammation; irritable bowel syndrome; nerve structures; otilonium bromide; rat colon; smooth muscle cells