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Background: We studied the effects of tachykinin receptor antagonists on fluid-induced, spontaneous net aboral propulsive complexes in isolated, vascularly perfused porcine ileal segments., Methods: Fluid was instilled at a constant rate into the proximal opening of the segment, resulting in regular, rapidly propagating propulsive complexes along the entire ileal segment in the aboral direction., Results: NKI, NK2 or NK3 receptor antagonists (CP99994, SR48968 and SR 142801 all at 10(-6) M) had no effect on the frequency of propulsive complexes. Atropine (10(-6) M) abolished the propulsive complexes for 15.0 +/- 1.3 min (n = 18). In spite of continued atropine infusion, the propulsive complexes reappeared. Infusion of the NK1 receptor antagonist CP99994 (10(-6) M) during continued atropine infusion blocked net aboral propulsive complexes in 5 experiments for 12.2 +/- 2.4 min and resulted in motor paralysis in 2 experiments. SP release, measured in the venous effluent, was significantly increased in relation to propulsive complexes during atropine infusion., Conclusion: We conclude that, in the porcine ileum, tachykinins mediate atropine-resistant net aboral propulsive complexes acting on NKI receptors.

Background: Glucagon-like peptide 2 (GLP-2) is produced in endocrine L-cells of the intestinal mucosa. Recently, GLP-2 was found to stimulate intestinal mucosal growth. Our objective was to study the content of GLP-2 in the large intestine in a murine model of T-cell-induced inflammatory bowel disease., Methods: Inflammation was induced by adoptive transfer of CD4+ blast T cells from BALB/c mice to SCID mice. The amount of GLP-2 (1-33) was measured with a specific, NH2-terminally directed radioimmunoassay in tissue extracts from the large intestine of transplanted mice developing colitis and from BALB/c and SCID control mice., Results: In the middle and descending colon segments showing the most severe signs of inflammatory lesions in the CD4+ T-cell-transplanted mice, the amount of GLP-2 was significantly lower than in similar colon segments in both untransplanted SCID mice and normal BALB/c mice (P = 0.0013 and 0.0033). In the descending colon the amount of GLP-2 was 6.7 +/- 1.0 pmol/g protein in the CD4+ transplanted mice compared with 68.4 +/- 20.3 and 42.7 +/- 4.3 in the two groups of control mice. Similar findings were made with regard to the contents of the two other proglucagon-derived intestinal peptides, glicentin and GLP-1., Conclusion: The amount of GLP-2 is markedly reduced in the colon of mice with a T-cell-induced inflammatory bowel disease histopathologically resembling both Crohn disease and ulcerative colitis. This observation may provide a pathophysiologic rationale for administration of GLP-2 as a trophic factor in inflammatory bowel disease.