21. EFFECT OF AGE AND SITE ON BASAL AND E.COLI ST-STIMULATED INTESTINAL GUANYLATE CYCLASE ACTIVITY IN CHILDREN

Abstract

E.Coli heat-stable enterotoxin (ST) induces diarrhea through the stimulation of the guanylate cyclase (GC)-cGMP system. The effect of ST on the human intestine has not been investigated nor is any information available on the activity, distribution, or development of GC activity in the human intestine. We have characterized these aspects of GC activity by measuring its basal and ST-stimulated activity in intestinal specimens, obtained operatively from 35 infants and children of 1 day to 16 years of age. GC activity was linear with protein concentration and time. Basal activity was similar in small intestine and in colon. In the small intestine, however, basal GC activity varied with age. It was maximal in children 1 day of age, then decreased linearly with age up to 8 months and became quite variable thereafter. In colon, an age-related pattern was not found. E.Coli ST stimulated GC activity in a dose-related manner. The effect of ST was linear with protein concentration and with time. In the small intestine, ST-stimulation of GC was twice that found in colon. Age affected the response of small intestinal GC to ST. Maximal response to ST was observed in children of 1 day of age and ST stimulation was significantly greater in children less than 1 year of age than in older children. In the colon, the response of GC to ST did not rhange with age. The greater responsiveness of small intestinal GC to ST in younger children may explain the severity of diarrhea induced by ST at that age.