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Decrease in activity of smooth muscle L-type Ca2+ channels and its reversal by NF-kappaB inhibitors in Crohn's colitis model.

Kazuya Kinoshita·Koichi Sato·Masatoshi Hori·Hiroshi Ozaki·Hideaki Karaki
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Abstract

We investigated the mechanisms of dysmotility of the colonic circular muscle of the Crohn's disease rat model. Contractions induced by KCl, carbachol, and Bay K 8644 were decreased in circular smooth muscles isolated from 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat colon. However, the absolute force and Ca2+ sensitivity of contractile proteins were not affected as assessed in alpha-toxin permeabilized smooth muscle. The current density of the L-type Ca2+ channel in circular smooth muscle cells was significantly decreased in the TNBS-treated colonic cells. However, expressions of the L-type Ca2+ channel mRNA and protein did not differ between control and TNBS-treated preparations. Pretreatment with the NF-kappaB inhibitors pyrrolidinedithiocarbamate and sulfasalazine partially recovered the decreased contractility and current density of the L-type Ca2+ channel by TNBS treatment. These results suggest that the decrease in the contraction of circular smooth muscle isolated from TNBS-induced colitis rat colon, which may be related to gut dysmotility in Crohn's disease, is attributable to the decreased activity of the L-type Ca2+ channel. The dysfunction of the L-type Ca2+ channel may be mediated by NF-kappaB-dependent pathways.

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AnimalsCalcium Channels, L-TypeColitisCrohn DiseaseElectric ConductivityEnzyme InhibitorsGastrointestinal MotilityIntestinal MucosaIntestinesMaleMuscle, SmoothNF-kappa BProlineRatsRats, Sprague-DawleySulfasalazineThiocarbamatesJournal ArticleResearch Support, Non-U.S. Gov't

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Kazuya Kinoshita, Koichi Sato, Masatoshi Hori, Hiroshi Ozaki, Hideaki Karaki. 2003-03-19. Decrease in activity of smooth muscle L-type Ca2+ channels and its reversal by NF-kappaB inhibitors in Crohn's colitis model.. https://doi.org/10.1152/ajpgi.00038.2003

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