Possible role of orexin A in nonadrenergic, noncholinergic inhibitory response of muscle of the mouse small intestine

Satoh, Yuji; Uchida, Mitsuhiro; Fujita, Akikazu; Nishio, Hideaki; Takeuchi, Tadayoshi; Hata, Fumiaki

doi:10.1016/s0014-2999(01)01339-5

Cited by 25 publications

(15 citation statements)

References 15 publications

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“…The mediator of NANC relaxation in the mouse intestine has been studied extensively in longitudinal muscle (Young et al, 1996;Satoh et al, 1999;Satoh et al, 2001;Mukai et al, 2002). In a previous study, we first examined the mediators of ascending contraction and descending relaxation (responses mainly reflected by those of circular muscle) in the mouse ileum.…”

Section: Discussionmentioning

confidence: 99%

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal

Okishio

Takeuchi

Fujita

et al. 2005

J. Smooth Muscle Res.

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Recently an essential role of interstitial cells of Cajal (ICC) within myenteric plexus (ICC-MY) was suggested in ascending contraction and descending relaxation in the mouse ileum. The role of ICC in these neural reflexes was examined in the distal colonic segments prepared from the wild type and c-kit mutant, W/W V mice, in the present study. Localized distension of the segments from the wild type mice by using a small balloon resulted in ascending contraction and descending relaxation. In the segments from the mutant mice, localized distension also induced these neural reflexes similar to those observed in the wild type mice. Immunohistochemical examination demonstrated that ICC-MY and ICC present in muscle layers (ICC-IM) were severely disrupted in the mutant mouse, but only ICC, present within submucosal plexus (ICC-SMP), remained unchanged. In the small strips with ICC-SMP absent prepared from the mutant mouse, electrical field stimulation induced contraction or relaxation in the absence or presence of atropine, respectively. It was suggested that ICC have no important role in the ascending and descending neural reflexes in the mouse distal colon, this is in direct contrast to the role of ICC-MY in the ileum.

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Section: Discussionmentioning

confidence: 99%

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal

Okishio

Takeuchi

Fujita

et al. 2005

J. Smooth Muscle Res.

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“…As described in a previous report (25), segments of the ileum were suspended in an organ bath containing 4 ml of Tyrode solution maintained at 37°C and bubbled with a mixture of 95% O2-5% CO2. One end of each segment was attached to an isotonic transducer (TD-112A; Nihonkohden, Tokyo, Japan), and the other end was mounted on an anodal electrode placed at the bottom of the bath.…”

Section: Methodsmentioning

confidence: 99%

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

Takeuchi

Tanaka²,

Nakajima³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Takeuchi T, Tanaka K, Nakajima H, Matsui M, Azuma Y-T. M 2 and M3 muscarinic receptors are involved in enteric nervemediated contraction of the mouse ileum: findings obtained with muscarinic-receptor knockout mouse. Am J Physiol Gastrointest Liver Physiol 292: G154 -G164, 2007; doi:10.1152/ajpgi.00173.2006.-The involvement of muscarinic receptors in neurogenic responses of the ileum was studied in wild-type and muscarinic-receptor (Mreceptor) knockout (KO) mice. Electrical field stimulation to the wild-type mouse ileum induced a biphasic response, a phasic and sustained contraction that was abolished by tetrodotoxin. The sustained contraction was prolonged for an extended period after the termination of electrical field stimulation. The phasic contraction was completely inhibited by atropine. In contrast, the sustained contraction was enhanced by atropine. Ileal strips prepared from M2-receptor KO mice exhibited a phasic contraction similar to that seen in wild-type mice and a sustained contraction that was larger than that in wild-type mice. In M3-receptor KO mice, the phasic contraction was smaller than that observed in wild-type mice. Acetylcholine exogenously administrated induced concentration-dependent contractions in strips isolated from wild-type, M2-and M3-receptor KO mice. However, contractions in M3-receptor KO mice shifted to the right. The sustained contraction was inhibited by capsaicin and neurokinin NK2 receptor antagonist, suggesting that it is mediated by substance P (SP). SP-induced contraction of M2-receptor KO mice did not differ from that of wild-type mice. SP immunoreactivity was located in enteric neurons, colocalized with M 2 receptor immunoreactivity. These results suggest that atropine-sensitive phasic contraction is mainly mediated via the M 3 receptor, and SP-mediated sustained contraction is negatively regulated by the M2 receptor at a presynaptic level.M2-and M3-receptor knockout mouse; neurogenic response; acetylcholine-mediated phasic contraction; substance P-mediated tonic contraction ACETYLCHOLINE (ACh) is released from cholinergic nervous terminals in the myenteric plexus, resulting in the contraction of intestinal smooth muscle through activation of muscarinic (M) receptors (9). Five subtypes of M receptors have so far been identified (39). It is well known that M 2 and M 3 receptors are present on the smooth muscle cells of gastrointestinal tracts and are expressed at ratios of 70 -80% and 20 -30%, respectively (6). A role of both M receptors in smooth muscle contraction was indicated by the examination of the effects of M-receptor subtype-specific antagonists on the contraction induced by exogenous M-receptor agonists (7). In the guinea pig and canine ileum, contractions induced by various Mreceptor agonists (carbachol, muscarine, and methacholine) were most strongly inhibited by the M 3 -receptor antagonist 4-diphenylacetoxy-N-methyl-piperidine methiodide (12, 27). In contrast, activation of the M 2 receptor in rat and guinea pig ileum was reported to inhibit isoproterenol...

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“…On intestine smooth muscle cells that express orexin receptors, [102] the direct effects of orexin may involve the activation of the Gq-PLC-IP 3 -Ca 2 + pathway, where elevated cytosolic Ca 2 + activates nitric oxide synthase (nNOS and eNOS are both Ca 2 + dependent) to generate the relaxant nitric oxide. Physiological studies of the effect of orexins on intestinal motility yield conflicting results.…”

Section: Neurophysiology Of the Orexin Systemmentioning

confidence: 99%

Orexin Receptor Antagonists: A New Concept In CNS Disorders?

et al. 2010

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Possible role of orexin A in nonadrenergic, noncholinergic inhibitory response of muscle of the mouse small intestine

Cited by 25 publications

References 15 publications

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal

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

Orexin Receptor Antagonists: A New Concept In CNS Disorders?

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Possible role of orexin A in nonadrenergic, noncholinergic inhibitory response of muscle of the mouse small intestine

Cited by 25 publications

References 15 publications

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal

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

Orexin Receptor Antagonists: A New Concept In CNS Disorders?

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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