Figure 6.

Colonic transit measurements in vitro (A) and in vivo (B, C) in wild-type (WT) and peptide knockout mice, in the absence or presence of Y₁ or Y₂ receptor antagonists Values are the mean + SEM from mice of different genotypes. In A, Y₁ receptor blockade (BIBO3304, 300 nM) inhibited colonic transit in all the genotypes but this was only significantly different from vehicle controls in NPY^−/− colon (*P≤ 0.05). Y₂ receptor antagonism with BIIE0246 (1 µM) significantly increased WT colonic transit compared with the effect of BIBO3304 (one-way anova, *P≤ 0.05). This difference in WT tissues between antagonist effects was absent from all peptide null mice, significantly so in NPY^−/− (P≤ 0.05, two-way anova). In B, the FPO observed in NPY^−/− mice was significantly increased compared with all other genotypes after 15 min in a novel environment (*P≤ 0.05, two-way anova). In C, acclimatized, vehicle-treated, NPY^−/− mice exhibited a trend for greater FPO, but this and the effects of Y₁ or Y₂ receptor antagonists were not significantly different from WT rates of defaecation (two-way anova).