Mechanical activity of small and large intestine in normal and mdx mice: a comparative analysis

Abstract

The aim of this study was to compare the motor pattern (recorded as changes in intraluminal pressure) of isolated duodenum and proximal colon between dystrophic mdx and normal mice. When duodenal recordings from control preparations were compared with mdx mice there was no significant difference in the spontaneous motor pattern, responses to electrical nerve stimulation or sensitivity to pharmacological agents. Colonic segments from mdx mice showed a more complex motor pattern, consisting of contractions with amplitude and frequency similar to those of controls and by additional contractions with lower amplitude and higher frequency. Moreover, 70% of the colonic preparations from mdx mice developed active tone. TTX (1 microM), both in control and in mdx mice, changed the motor pattern, revealing regular rhythmic contractions similar in both preparations. L-NAME (100 microM) in both preparations increased contractile activity, revealing additional low contractions in control and potentiating them in mdx colon. In both control and mdx mice, inhibitory responses elicited by electrical field stimulation (EFS) were significantly attenuated by L-NAME. Our results provide evidence for the presence of a different motor pattern in mdx proximal colon and suggest that mdx mice can be considered a suitable animal model for investigating the dystrophic process.

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

“…The weak inhibition of NOS by 10 µM L-NAME accelerated MMC (Fig. 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].…”

“…Contractility of the colonic smooth muscle in mdx mouse is very likely to be normal because there is no difference in the amplitude of TTX-sensitive rhythmic contractions between mdx and control colon [16], and because mdx colon produces a transient contraction in response to the application of carbamylcholine (50 µM), an agonist of the muscarinic receptor, that is similar to that in the control colon [19]. As discussed previously, however, n-NOS in the colonic smooth muscle cell may modulate the MMC pacemaker in the myenteric nerve; the deficit in the smooth muscle n-NOS in mdx colon may reduce the modulation of the MMC pacemaker.…”

“…Studies with distal colon segments from an animal model of DMD, the muscular dystrophy (mdx) mouse, demonstrated a frequent generation of abnormal MMC that were interposed between normal orthodromic MMC [14,15], as well as an abnormally high level of tone [16,17]. The expressions of e-, i-, and n-NOS in the myenteric nerve, the ICC, and the smooth muscle cells was similar in the mdx and control colon, except for a lower expression of n-NOS in the mdx smooth muscle cells [12].…”

Role of cholinergic neurons in the motor effects of glucagon-like peptide-2 in mouse colon

“…Thus the effects of increasing concentrations of GLP-2 were evaluated after pretreatment of intestinal preparations with N -nitro-L-arginine methyl ester (L-NAME) (300 M), an inhibitor of nitric oxide (NO) synthase; apamin (0.1 M), a blocker of small conductance Ca 2ϩ -dependent K ϩ channels; [Lys1,Pro2,5,Arg3,4,Tyr6]VIP , a VIP receptor antagonist; atropine (1 M), a muscarinic receptor antagonist; or pertussis toxin (PTX) (300 ng/ml), a G i/o protein inhibitor. These agents were added to the perfusing solution at least 30 min before testing of the peptide, except PTX, which was left in contact with the tissue for 3 h. The concentrations of the inhibitors used were determined from previous experiments in which they have been shown to be effective in mouse colon or from literature (1,15,18,26).…”

“…The mechanical activity was recorded as previously described (18). In brief, the distal end of each segment was tied around the mouth of a J tube, which was connected via a T catheter to a pressure transducer (Statham mod.…”