Functional role of inducible nitric oxide synthase on mouse colonic motility

Mancinelli, R.; Fabrizi, Adele; Vargiu, Romina; Morrone, Luigi Antonio; Bagetta, Giacinto; Azzena, Gian Battista

doi:10.1016/s0304-3940(01)02156-5

Cited by 15 publications

(24 citation statements)

References 9 publications

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“…10A), as reported previously [15,16]. In contrast, a strong inhibition of i-NOS by DPI inhibited MMC, which is consistent with previous results [30]. Further, 1,3-PBIT with K i = 0.049, 0.25, and 9 µM for the inhibition of i-, n-, and e-NOS, respectively [22], completely inhibited MMC at a concentration of 5 µM (Figs.…”

Section: Discussionsupporting

confidence: 92%

The Effect of e-, i-, and n-Nitric Oxide Synthase Inhibition on Colonic Motility in Normal and Muscular Dystrophy (Mdx) Mice

Tameyasu

Ogura

Ogihara

2004

JJP

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(5 µM) reduced the magnitude of local, rhythmic contractions (LC) paced by the interstitial cells of Cajal (ICC), but 1,3-PBIT (50 µM) increased their magnitude. There was no difference in the effect of spermine and 1,3-PBIT on the LC between mdx and control colon. The results suggest an inhibition of MMC by high concentrations of e-, i-, and n-NOS inhibitors, modulation of ICC activity by e-NOS, and greater susceptibility of MMC to n-NOS inhibition in the mdx proximal than in the control colon, which is very likely because of a deficit in n-NOS in the mdx smooth muscle affecting the MMC pacemaker. A deficit in the effect of mdx smooth muscle n-NOS on an MMC pacemaker may be the origin of diarrhea or constipation in human DMD. Japanese Journal of Physiology Vol. 54, [555][556][557][558][559][560][561][562][563][564][565][566] 2004 Abstract: To explore the origin of diarrhea or constipation in human Duchenne muscular dystrophy (DMD), the effect of the inhibition of e-, i-, and n-nitric oxide synthase (NOS) on the motility of proximal and distal segments of colon of muscular dystrophy (mdx) and control mice was studied. The frequency of migrating motor complexes (MMC) was higher in the proximal than in the distal segments in mdx colon (0.56 vs. 0.25 cpm) and in the control colon (0.7 vs. 0.25 cpm), and there was no difference when mdx was compared to control segments. High concentrations of NOS inhibitors, including 1,3-PBIT dihydrobromide (1,3-PBIT) and spermine, inhibited MMC. The dose of spermine required to inhibit MMC was lower for the proximal mdx colon than for the distal mdx or control colon. In the presence of tetrodotoxin, spermine (1 mM) and 1,3-PBIT

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Section: Discussionsupporting

confidence: 92%

The Effect of e-, i-, and n-Nitric Oxide Synthase Inhibition on Colonic Motility in Normal and Muscular Dystrophy (Mdx) Mice

Tameyasu

Ogura

Ogihara

2004

JJP

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“…In different regions of the gastrointestinal tract of these patients, important motility disorders such as gastric dilatation, dysphagia, vomiting, and intestinal pseudo-obstruction, have been reported (Barohn et al 1988;Yoshida et al 1988;Bensen et al 1996). In these animals, an altered gastric and colonic motility, considered to be neuronal (Azzena and Mancinelli 1999;Mulè et al 1999;Baccari et al 2000;Serio et al 2001) and/or muscular in origin (Mancinelli et al 2001;Mulè et al 2001), was found. In these animals, an altered gastric and colonic motility, considered to be neuronal (Azzena and Mancinelli 1999;Mulè et al 1999;Baccari et al 2000;Serio et al 2001) and/or muscular in origin (Mancinelli et al 2001;Mulè et al 2001), was found.…”

Section: Introductionmentioning

confidence: 90%

Interstitial cells of Cajal, enteric neurons, and smooth muscle and myoid cells of the murine gastrointestinal tract express full-length dystrophin

Vannucchi¹,

Zardo²,

Corsani³

et al. 2002

Histochem Cell Biol

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A gene located on the X chromosome is responsible for the transcription of several mRNA and related dystrophin isoforms. Lack or truncated expression of the 427-kDa, full-length isoform in skeletal muscle results in Duchenne muscular dystrophy (DMD). Patients with DMD, as well as mdx mice, a mutant strain also lacking this isoform, show gastrointestinal dismotilities. The present aim was to identify the cell types that express full-length dystrophin in the gastrointestinal tract. An immunohistochemical study was performed using an antibody specific for this isoform, and double labelings were made for interstitial cells of Cajal (ICC) identification and to verify whether all neurons express full-length dystrophin. Three different fixation procedures were used. The results showed that ICC, enteric neurons, and smooth muscle and myoid cells expressed full-length dystrophin. In ICC and neurons, dystrophin-immunoreactive patches were irregularly distributed at the cell contour and within the cytoplasm. In smooth muscle and myoid cells, regularly spaced dystrophin-immunoreactive bars were located along the cell contour. Labeling intensity varied according to fixation procedure. The different subcellular distributions of dystrophin immunoreactivity might reflect diverse roles played by full-length isoforms in each cell type. Dystrophin loss in cells involved in gastrointestinal motility might explain the gastrointestinal symptomatology affecting DMD patients and mdx mice.

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“…Several NOS inhibitors, which have been used to demonstrate the functional roles of endogenous NO, are as follows: N G -monomethyl-L-arginine (L-NMMA) (Palmer et al, 1988), N G -nitro-L-arginine (L-NA) (Rees et al, 1990;Toda et al, 1990), L-NA methyl ester (L-NAME) (Rees et al, 1990), and asymmetric dimethylarginine (ADMA) (Vallance et al, 1992) as nonselective inhibitors; 7-nitroindazol (7-NI) (Moore et al, 1993) as a relatively selective inhibitor against nNOS; and aminoguanidine (Griffiths et al, 1993), N 6 -iminoethyl-L-lysine (Moore et al, 1994), and W1400 (Mancinelli et al, 2001) as iNOSselective inhibitors.…”

mentioning

confidence: 99%