Figure 5.
CFTRact-J027 actions on intestinal fluid secretion, absorption, and motility. (A) Whole-gut transit time in control and loperamide-treated wild-type (left) and cystic fibrosis (right) mice (means ± SEM, 3–5 mice per group). Where indicated, loperamide (0.3 mg/kg) and CFTRact-J027 (10 mg/kg) were administered IP at 0 time (means ± SEM, 6 mice per group). (B) Contraction of isolated intestinal strips. Ileum and colon strips (∼2 cm) were suspended in Krebs–Henseleit buffer with 0.5 g and 0.2 g tension, respectively. Where indicated, CFTRact-J027, loperamide, and carbachol were added to the organ chamber. (C) Intestinal fluid secretion was measured in closed midjejunal loops in wild-type mice (upper panel). Loops were injected with 100 μL vehicle or 100 μg CFTRact-J027. Loop weight/length was measured at 90 minutes (means ± SEM, 4 loops per group). Similar experiments were performed in cystic fibrosis mice (lower panel, 4 loops per group). (D) Intestinal fluid absorption was measured in midjejunal loops in cystic fibrosis mice. Loops were injected with 100 μL vehicle or 100 microgram CFTRact-J027. Loop weight/length was measured at 30 minutes. Summary of fluid absorption (means ± SEM, 4 loops per group). One-way analysis of variance was used for panel A , Student's t test was used for panel C and D. ∗∗P < .01, ∗∗∗P < .001.