M2 and M3 muscarinic receptors are involved in enteric nerve-mediated contraction of the mouse ileum: findings obtained with muscarinic-receptor knockout mouse

Takeuchi, Tadayoshi; Tanaka, Keisuke; Nakajima, Hidemitsu; Matsui, Masanao; Azuma, Yasutaka

doi:10.1152/ajpgi.00173.2006

Cited by 33 publications

(36 citation statements)

References 40 publications

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“…However, other studies indicate that in carbachol-induced ileal smooth muscle contraction, only low-dose induced contraction involves M2 receptors (Unno et al, 2005), and that although M2 receptors are involved in sustained carbachol-induced contraction of longitudinal smooth muscle of the mouse ileum, they are not involved in transient contractions (Takeuchi et al, 2006). These findings suggest that the observed differences in contractile responses to inflammation between circular and longitudinal smooth muscle may not be fully explained by the degree of dependence on different muscarinic receptor isoforms.…”

Section: Muscarinic Receptor Activity Is Changed In Intestinal Inflammentioning

confidence: 96%

Mechanism of abnormal intestinal motility in inflammatory bowel disease: how smooth muscle contraction is reduced?

Ohama

Hori

Ozaki

2007

J Smooth Muscle Res

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Intestinal inflammation alters the contractile activity of intestinal smooth muscle. Motility disorders of the gastrointestinal tract are clinically important symptoms, because they are often associated with severe interstitial inflammation. In addition, the motility disorders secondarily induce abnormal growth of the intestinal flora, and the resulting disturbance of this flora aggravates the pathogenesis of mucosal inflammation. This in turn aggravates the intestinal dysmotility; i.e., it is an inflammatory spiral. Therefore, it is important to elucidate the mechanisms involved in the changes in motor function which occur in intestinal inflammation. Recent studies have revealed several molecular mechanisms responsible for the decreased motility which occurs in an inflamed gastrointestinal tract. In the present review, we discuss the functional failure of smooth muscle cells, including changes in the activity of muscarinic receptors, ion channels and the endogenous myosin phosphatase inhibitor CPI-17.Key words: intestinal inflammation, smooth muscle, contraction, CPI-17 Motility disorders in intestinal inflammationMotility disorders of the gastrointestinal tract are extremely important clinically because they can lead to systemic disease. In humans and in animal models, intestinal inflammation results in the disturbance of motility, which may reflect changes in smooth muscle function and/or the enteric nervous system (Vermillion et al., 1993;Vrees et al., 2002). Both increased and decreased smooth muscle contractility has been observed in intestinal inflammation. In a model of nematode infection-induced gut inflammation, such as Trichinella spiralis infectioninduced gut inflammation, smooth muscle contractility is increased (Vermillion and Collins, 1988;Blennerhassett et al., 1992). On the other hand, smooth muscle contractility is decreased T. OHAMA et al. 44 in the intestinal inflammation induced by trinitrobenzene sulphonic acid (TNBS), surgical manipulation, experimental obstruction, hemorrhagic shock, or peritonitis (Kalff et al., 1998;Moreels et al., 2001; Koyluoglu et al., 2002;Hierholzer et al., 2004; Kinoshita et al., 2006; Kiyosue et al., 2006;Won et al., 2006; Kinoshita et al., 2007;Ohama et al., 2007b). These differences in contractile responses may be due to differences in cytokine profiles. Reports from the Collins group (Akiho et al., 2002;Akiho et al., 2005a;Akiho et al., 2005b) have suggested that nematode-induced hypercontractility is mediated by an increase in prostaglandin E2 (PGE2) levels after induction of the expression of Th2 cytokines such as interleukin (IL)-4 and IL-13.On the other hand, reports suggest that TNBS-induced gut inflammation is mediated mainly by Th1 cytokines such as IL-1β, tumor necrosis factor-α (TNF-α) and IL-12 (Neurath et al., 1995; Kinoshita et al., 2006; Kiyosue et al., 2006;Ohama et al., 2007b). In this review, we focused on the molecular mechanisms that are responsible for the decreased motility of the inflamed intestine. Nematode-induced hyper-co...

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Section: Muscarinic Receptor Activity Is Changed In Intestinal Inflammentioning

confidence: 96%

Mechanism of abnormal intestinal motility in inflammatory bowel disease: how smooth muscle contraction is reduced?

Ohama

Hori

Ozaki

2007

J Smooth Muscle Res

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“…Frozen sections (5 mm thick) were cut and prepared for immunofluorescent and immunohistochemistry staining (Takeuchi et al, 2007). Expression of PACAP was detected using rabbit anti-PACAP antibody (Peninsula Laboratories, Inc., San Carlos, CA).…”

Section: Immunohistochemical Studymentioning

confidence: 99%

PACAP provides colonic protection against dextran sodium sulfate induced colitis

Azuma

Hagi

Shintani

et al. 2008

Journal Cellular Physiology

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Pituitary adenylate cyclase-activating polypeptide (PACAP) plays a crucial role in immunity and inflammation. Our aim was to obtain insight in the role of PACAP in experimental colitis in mice and thus its possible role in inflammatory bowel disease. PACAP-deficient (PACAP-/-) mice and wild-type control mice were challenged by colitis-inducing agent, dextran sulfate sodium (DSS). We monitored clinical symptoms, intestinal morphology, and difference of cytokine production in the proximal and distal colon. After DSS administration, mortality was more severe in PACAP-/- mice versus wild-type control mice. The histological score and the disease activity index of PACAP-/- mice were significantly higher than those of wild-type control mice. In proximal colon, production of IL-1beta and IL-6 in PACAP-/- mice were significantly upregulated on day 8 after DSS administration, compared to wild-type control mice. In distal colon, furthermore, production of IFNgamma, IL-1beta, IL-6, IL-12, and KC were significantly higher in PACAP-/- mice than in wild-type control mice on day 4. Our findings indicate that PACAP regulates the production of pro-inflammatory cytokine in the experimental colitis.

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“…The responses to electrical field stimulation (EFS) were measured using previously described methods [24,25]. Briefly, the distal colon was removed from mice (10-15 weeks old).…”

Section: Methodsmentioning

confidence: 99%

Na+/Ca2+ Exchanger 1 Transgenic Mice Display Increased Relaxation in the Distal Colon

et al. 2014

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Na⁺/Ca²⁺ exchanger 1 (NCX1) is a plasma membrane transporter involved in regulating intracellular Ca²⁺ concentrations. NCX1 is critical for Ca²⁺ regulation in cardiac muscle, vascular smooth muscle and nerve fibers. However, little is known about the physiological role of NCX1 in gastrointestinal motility. To determine the role of NCX1 in gastrointestinal tissues, we examined electric field stimulation (EFS)-induced responses in the longitudinal smooth muscle of the distal colon in smooth muscle-specific NCX1 transgenic mice (Tg). Tg show that NCX1 protein was overexpressed in the distal colon at a level twofold greater than that of endogenous NCX1. We found that the amplitudes of EFS-induced relaxation that persisted during EFS were greater in Tg than in wild-type mice (WT). Under the nonadrenergic, noncholinergic condition, the EFS-induced relaxation in Tg was also greater than that in WT. Inhibition of NO synthase, CO synthase, soluble guanylate cyclase (sGC), and protein kinase G (PKG) all attenuated the enhanced relaxation in Tg, demonstrating the importance of NCX1 in NO/sGC/PKG signaling. The action of NOR-1, an NO donor, induced enhanced relaxation in Tg compared with that in WT. Unlike NOR-1, pituitary adenylate cyclase-activating peptide and vasoactive intestinal peptide induced a similar relaxation in Tg compared with that in WT. In this study, we demonstrate that NCX1 plays an important role in smooth muscle motility in the mouse distal colon. i 2014 S. Karger AG, Basel

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M₂ and M₃ muscarinic receptors are involved in enteric nerve-mediated contraction of the mouse ileum: findings obtained with muscarinic-receptor knockout mouse

Cited by 33 publications

References 40 publications

Mechanism of abnormal intestinal motility in inflammatory bowel disease: how smooth muscle contraction is reduced?

Mechanism of abnormal intestinal motility in inflammatory bowel disease: how smooth muscle contraction is reduced?

PACAP provides colonic protection against dextran sodium sulfate induced colitis

Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger 1 Transgenic Mice Display Increased Relaxation in the Distal Colon

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