Fig. 7. Gdnf^+/–, Nrtn^–/–, Gdnf^+/–/Nrtn^–/–, Gfra1^+/– and Ret^+/– mice all have abnormal intestinal contractility and reduced VIP and substance P release. Contractility of intestinal circular (A,B) and longitudinal (C,D) muscle in response to electric field stimulation. Different colored bars, as indicated in H, represent distinct mouse genotypes. (A-D) Intestinal segments from the small bowel (A,C) or colon (B,D) were stimulated with a 1 minute electric field stimulus at 80 V and 0.5, 1.0, 5.0 or 10.0 Hz. Contractile strength was measured with force transducers. Small bowel circular (A) and longitudinal (C) muscle, as well as colon circular muscle (B), contract during electric field stimulation. Colon longitudinal muscle relaxes during field stimulation, and then has a rebound contraction. The colon longitudinal muscle data (D) plots the rebound contraction phase. The relaxation phase that occurs during electric field stimulation was also reduced in all genotypes compared with wild-type mice, but the data are omitted to simplify the figure. Release of VIP (E,F) and substance P (G,H) from the small intestine (E,G) or colon (F,H) was measured either in the basal state or after electric field stimulation. The bars for transmitter release in response to electric field stimulation represent the increase in transmitter release over baseline. Error bars show s.e.m.. All of the mutant genotypes differ from wild type for all of the contraction and transmitter release parameters measured (P<0.05).