Neurogenic contraction of mouse rectum via the cyclooxygenase pathway: Changes of PGE2-induced contraction with dextran sulfate sodium-induced colitis

Decrease of guanylyl cyclase β1 subunit and nitric oxide (NO)-induced relaxation in mouse rectum with colitis and its reproduction on long-term NO treatment

“…Treatment with indomethacin or diclofenac reduced the ESinduced contraction by half. A greater part of the contraction (over 80%) was inhibited by co-treatment with atropine and indomethacin in the present study, as previously observed under different conditions (Hamada et al 2010). Treatment with MK886, an inhibitor of 5-lipoxygenase activating protein, at 10 μM did not modify the ES-induced responses b Role of the NO pathway in ES-induced responses in rectum.…”

“…Approximately 10% of the animals had more than a 25% weight loss, but these animals were discarded. Under our conditions, myeoperoxidase activity increased similar in both rectum and distal colon (Hamada et al 2010). Inflammation extent/severity (from 0 to 3) and epithelial damage (from 0 to 4) were determined as the histological parameters of colitis in accordance with previous reports (Kudo et al 2008;Van Crombruggen et al 2008): the scores were grade 2.2 ± 0.4 (moderate extent) and 2.5 ± 0.5 (crypt damage over 70% in large areas), respectively, in both regions (n = 6).…”

“…Thus, an isotonic response was examined in some experiments, and data are expressed as a percentage of the contraction induced by 3 μM ACh (% of ACh contraction). Spontaneous contraction has two (phasic and tonic) components, and the resting tone reflecting tonic contractile activity was not changed by DSS treatment as shown (Murakami et al 2009;Hamada et al 2010). Thus, the phasic response, a maximal difference between the peak and the lowest values in the presence of vehicle, was described as a spontaneous contraction in this study.…”

“…Previously, we reported that the ES-induced contraction in rectum from mice with DSS-induced colitis was decreased compared with control levels (Hamada et al 2010). The ES used in that study caused only a contractive response, no relaxation, in rectum from control mice.…”

“…For treatment with the inhibitors or receptor antagonists, the preparations were incubated for the period indicated with the reagents, after which the contractile response was measured in the presence of the respective reagents. The inhibitors or antagonists were used at concentrations reported previously (Murakami et al 2009;Hamada et al 2010). A stimulator (Sen-7203, Nihon Koden, Tokyo) was used for transmural ES of the rectum, and the preparations were stimulated by platinum needlering (a ring was placed 20 mm above the base of a needle 5 mm in length) electrodes.…”