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 role of endogenous tachykinins and the mechanisms whereby they act on NK2 receptors, modulating spontaneous motility, were investigated in rat isolated proximal colon. The mechanical activity was detected as changes in intraluminal pressure. The NK2 receptor antagonist, MEN 10627, produced a concentration-dependent reduction of the contraction amplitude. [beta-Ala8]-neurokinin A(4-10), an NK2 receptor agonist, and [Sar9, Met(O2)11]-Substance P ([Sar9, Met(O2)11]-SP), an NK1 receptor agonist, induced a concentration-dependent contractile response, characterized by an increase in basal tone with superimposed phasic contractions. MEN 10627 antagonized the response to [beta-Ala8]-neurokinin A(4-10), without affecting that to [Sar9, Met(O2)11]-SP. Tetrodotoxin (TTX), hexamethonium and Nomega-nitro-L-arginine methyl ester (L-NAME) significantly reduced the response to MEN 10627. The NK3 receptor agonist, senktide, was able to activate the nitrergic inhibitory pathway, as it induced a TTX-and L-NAME-sensitive inhibitory effect. [beta-Ala8]-neurokinin A(4-10) was able to antagonize the inhibitory response to senktide. These findings suggest that tachykinins acting on NK2 receptors play a role in the modulation of the spontaneous mechanical activity. The mechanism of this action would be, in part, acting directly on the smooth muscle cells, and, in part neurogenic, sustained by nicotinic inputs, and possibly due to inhibition of NO tonic release.