Intestinal kinetics and dynamics of Escherichia coli heat-stabile enterotoxin in suckling mice.
The heat-stabile enterotoxin produced by Escherichia coli (ST) induces diarrhea by binding to receptors on intestinal cells, activating guanylyl cyclase, and increasing cyclic GMP. High- and low-affinity receptors for this toxin have been identified previously. ST induces intestinal secretion in suckling mice in picomole doses, suggesting a role for high-affinity receptors in this process. The present studies examine the relative roles of high- and low-affinity receptors in this process. The time course of changes in free ST concentrations in suckling mouse intestine was determined after intragastric inoculation. Also, binding characteristics of high- and low-affinity receptors and their coupling to guanylyl cyclase were defined in intestinal membranes from suckling mice. Intestinal concentrations of toxin and receptor binding characteristics empirically determined were used in a dynamic model correlating fractional occupancy of high- and low-affinity receptors with intestinal secretion to estimate their relative contributions to ST-induced diarrhea.
Waldman
S A
SA
Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Phillips
K
K
Parkinson
S J
SJ
D000818:Animals; D000833:Animals, Suckling; D001427:Bacterial Toxins / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D001835:Body Weight; D004768:Enterotoxins / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D004789:Enzyme Activation; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins; D006162:Guanylate Cyclase / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009929:Organ Size; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D018000:Receptors, Peptide; C034151:heat stable toxin (E coli); D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled