Changes in the responsiveness of the colonic smooth muscle to carbachol in Hirschsprung's disease.
In vitro experiments were performed on smooth-muscle strips cut out in longitudinal and circular direction from the colon of Hirschsprung's patients who underwent an operation and from patients operated on for tumors of the sigmoid colon and rectum, serving as controls. The changes in the contractile activity of the smooth-muscle strips after carbachol applied cumulatively were examined and dose-response curves were plotted. The EC50 values for the circular strips from the aganglionic part of the colon were 6 x 10(-7) M in Hirschsprung's patients and 3.7 x 10(-8) M in control patients: the pD2 values were 6.23 and 7.43, respectively. This showed that the affinity of cholinoreceptors in the aganglionic part of the colon for carbachol was 16 times lower in Hirschsprung's patients as compared to control patients. The EC50 values for longitudinal strips from the ganglionic part of the colon were 2.6 x 10(-7) M in Hirschsprung's patients and 4 x 10(-8) M in control patients; pD2 values were 6.6 and 7.4, respectively. The affinity of cholinoreceptors in the smooth muscle of the ganglionic part of the colon for carbachol was also decreased (nearly 6.5 times) in Hirschsprung's patients as compared to controls.