Abstract
Children suffer a disproportionate share of the morbidity attributed to enterotoxigenic diarrhea. Receptor density on cell surfaces is known to effect the action of Cholera Toxin (CT). We hypothesize that structural changes during development in enterocyte membranes will modulate the binding and enterocyte response to CT. A complete randomized block design was used to compare the binding kinetics of CT to developing rat enterocyte microvillus membrane (MVM) prepared from newborn (NB), two week (2wk), four week (4wk) and adult (AD) animals. Enrichments of sucrase and lactase ranged from 9 to 22 fold. Saturation binding isotherms were generated on twelve independent samples (3 blocks) under conditions shown to be at steady state and reversible. Scatchard analysis suggested positive cooperative binding to a single class of receptor and tne isotherms were analyzed using both the Hill-Waud and Michael-is -Menton function. The Hill-Waud model explained significantly more of the observed data (P<.05-.001). Receptor density varied significantly by age (ANOVA F=4.62 P=.013) as did the “half” dissociation constant (Kh) (ANOVA model: F=6.28 P=.022 Age: F=7.48 P=.019). Neither receptor concentration nor membrane “purity” confounded these observations. Changes in binding affinity (Ka) paralleled changes in Kh. We conclude that receptor density and “affinity” change with postnatal age. We speculate that developmental differences in receptor density and binding affinity may partially explain the enhanced morbidity due to toxigenie diarrhea in children.
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Lencer, W., Chu, SH. & Walker, W. ALTERED BINDING KINETICS OF CHOLERA TOXIN TO DEVELOPING RAT MUCOSA. Pediatr Res 21 (Suppl 4), 272 (1987). https://doi.org/10.1203/00006450-198704010-00627
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DOI: https://doi.org/10.1203/00006450-198704010-00627