Mechanism of action of Escherichia coli heat stable enterotoxin in a human colonic cell line.
Escherichia coli heat stable enterotoxin (STa) caused Cl- secretion across T84 cell monolayers in a dose-dependent manner only when applied to the apical membrane surface and not when applied to the basolateral surface. Measurement of cAMP, cGMP, and free cytosolic Ca2+ in response to STa suggested that cGMP alone mediated the Cl- secretory response. Studies utilizing blockers of the Na+,K+-ATPase pump, a Na+,K+,Cl- cotransport system, a K+ channel, and a Cl- channel suggest that all of them participate in the Cl- secretory process induced by STa. The results suggest that the Cl- secretory response induced by STa is mediated by cGMP after the enterotoxin binds to its receptor on the apical membrane. The enterotoxin, by increasing cGMP, opens a K+ channel on the basolateral membrane as well as a Cl- channel on the apical membrane. The activation of these ion exit mechanisms, together with activations of the Na+,K+,Cl- cotransporter and the Na+,K+-ATPase pump drives Cl- exit through the Cl- channel on the apical membrane.
Huott
P A
PA
Department of Medicine, San Diego Medical Center, California 92103.
Liu
W
W
McRoberts
J A
JA
Giannella
R A
RA
Dharmsathaphorn
K
K
D001427:Bacterial Toxins / Q000494:pharmacology*; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002712:Chlorides / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000382:microbiology; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology*; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism
D001427:Bacterial Toxins; D002712:Chlorides; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007473:Ion Channels; C034151:heat stable toxin (E coli); D000242:Cyclic AMP; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium