The present results suggest that GLP-1 is able to act in the enteric nervous system by decreasing the excitatory cholinergic neurotransmission through presynaptic GLP-1Rs, which modulate NO release.
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.
This study examined whether alterations of the spontaneous and evoked mechanical activity are present in the stomach of the mdx mouse, the animal model for Duchenne muscular dystrophy. The gastric mechanical activity from whole-organ of normal and mdx mice was recorded in vitro as changes of intraluminal pressure. All gastric preparations developed spontaneous tone and phasic contractions, although the tone of the mdx preparations was significantly greater. Atropine reduced the tone of the two preparations by the same degree. Nomega-nitro-l-arginine methyl ester (l-NAME) significantly increased the tone and spontaneous contractions only in the stomach from normal animals, but did not affect on the mdx preparations. Effects ofl-NAME on tone and contractility were preserved in the presence of tetrodotoxin. In both types of tissues electrical field stimulation (EFS) induced a biphasic response: cholinergic contraction followed by slow relaxation. In nonadrenergic noncholinergic conditions, EFS induced a rapid relaxation followed by a slow component in both types of tissues. l-NAME abolished the rapid component, reduced the slow component and unmasked tachychinergic contractions. No significant difference was found in evoked responses. The enteric neurotransmission is preserved in mdx gastric preparations, although alterations in the ongoing production of nitric oxide are present.
1 The neurotransmitters involved in NANC relaxation and their possible interactions were investigated in mouse isolated stomach, recording the motor responses as changes of endoluminal pressure from whole organ. 2 Field stimulation produced tetrodotoxin-sensitive, frequency-dependent, biphasic responses: rapid transient relaxation followed by a delayed inhibitory component. 3 The inhibitor of the synthesis of nitric oxide (NO), l-NAME, abolished the rapid relaxation and significantly reduced the slow relaxation. Apamin, blocker of Ca 2 þ -dependent K þ channels, or ADPbS, which desensitises P 2y purinoceptors, reduced the slow relaxation to 2 -8 Hz, without affecting that to 16 -32 Hz or the fast relaxation. a-Chymotrypsin or vasoactive intestinal polypeptide 6 -28 (VIP6 -28), antagonist of VIP receptors, failed to affect the fast component or the delayed relaxation to 2 -4 Hz, but antagonised the slow component to 8 -32 Hz.
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