Premium
Supernatants of irritable bowel syndrome mucosal biopsies impair human colonic smooth muscle contractility
Author(s) -
Guarino M. P.,
Barbara G.,
Cicenia A.,
Altomare A.,
Barbaro M. R.,
Cocca S.,
Scirocco A.,
Cremon C.,
Emerenziani S.,
Stanghellini V.,
Cicala M.,
Severi C.
Publication year - 2017
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12928
Subject(s) - irritable bowel syndrome , contractility , medicine , endocrinology , contraction (grammar) , acetylcholine , muscle contraction , motility , biology , genetics
Background Changes in intestinal motility are likely to contribute to irritable bowel syndrome ( IBS ) pathophysiology. The aim of the study was to investigate the effects of IBS mucosal supernatants on human colonic muscle contractility. Methods Supernatants were obtained from biopsies of 18 IBS patients—nine with constipation ( IBS ‐C) and nine with diarrhea‐predominant IBS ( IBS ‐D)—and nine asymptomatic subjects, used as controls. Colonic circular smooth muscle strips or isolated cells ( SMC ) were exposed to control or IBS supernatants. Spontaneous phasic contractions on strips and morphofunctional parameters on cells were evaluated in basal conditions and in response to acetylcholine (Ach). Incubation with IBS supernatants was also conducted in the presence of antagonists and inhibitors (namely histamine, protease and prostaglandin antagonists, nuclear factor‐kappa B inhibitor, catalase, NADPH oxidase inhibitor, and the cAMP ‐ and/or cGMP ‐cyclase inhibitors). Key Results Exposure to IBS ‐C and IBS ‐D supernatants induced a significant reduction in basal tone and Ach‐elicited contraction of muscle strips and a significant shortening and impairment of Ach contraction of SMC s. The NADPH oxidase inhibitor prevented the effect of supernatants, while the protease antagonist only IBS ‐C effect. No effect was observed with the other antagonists and inhibitors. Dilution of IBS ‐D supernatants partially restored the effects only on SMC s, whereas dilution of IBS ‐C supernatants significantly reverted the effects on muscle strips and Ach‐elicited response on SMC . Conclusions & Inferences Supernatants from mucosal biopsies of IBS patients reduce colonic contractility. The observed impairment was concentration dependent, likely occurring through intracellular oxidative stress damage, involving different neuromotor mechanisms depending on the IBS subtype.