Mecanismes fisiopatològics implicats en la dismotilitat intestinal associada a enfermetats intestinals cròniques: síndrome de l'intestí irritable i enfermetat inflamatòria intestinal

Important disturbances in motility are associated to a number of chronic gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The aetiology of such disturbances has not been clearly established and so far palliative therapeutical resources are still of limited efficacy and important secondary effects. The aim of this proposal is to study the mechanisms involved in the occurrence of dismotility in models mimicking IBS and IBD, starting from peer knowledge of the control of gastrointestinal motility in physiological conditions. We intend to study 1) the role of mast cells as nexus between the immune system and the extrinsic nervous pathways; 2) the function of the enteric nervous system and the interstitial cell of Cajal network as regulators of pacemaker activity and smooth muscle contraction. W\super v\nosuper W\super v\nosuper, mutant rats-in which the c-kit receptor deficiency determines important changes in the development of both mast cells and interstitial cells of Cajal-will be used to study the involvement of both cell types in intestinal motility. Finally, we intend to study enteric neurotransmission and pacemaker activity in healthy specimens of human colon. In summary, this proposal is intended to obtain data relevant to be design of new therapeutic strategies addressed to improve motility disorsers associated to chronic gastrointestinal diseases