Calcium influx mediated by the Escherichia coli heat-stable enterotoxin B (STB).

Abstract

The al. (13, 14) indicates that STB induces a rapid short-circuit current across porcine intestinal mucosa. Evidence for chloride transport was not observed, yet electrogenic anion secretion, possibly bicarbonate, was observed in the absence of elevated cyclic nucleotides (14,15). Beyond these few studies, nothing is known of the mechanism of STB action.Evidence that suggests a receptor-mediated mode of STB action includes short-circuit current responses when toxin is delivered to the mucosal, but not serosal, side of intestinal tissue mounted in Ussing chambers (13); a rapid STB response in experiments utilizing either mounted tissue or whole animal models (15 min and 2 hr, respectively) (13,14,16); and the lack of apparent damage to the intestinal mucosa following STB treatment (17,18). Known mediators of membrane signal transduction include cAMP, cGMP, the phosphatidylinositol 4,5-bisphosphate-derived metabolites inositol 1,4,5-trisphosphate (InsP3) and diacyl glycerol, and Ca2W (for reviews, see refs. 19-21

Escherichia coli STb toxin induces apoptosis in intestinal epithelial cell lines

“…The activation of caspase-3 observed in our study could therefore be partially responsible for the influx of calcium observed during STb-mediated diarrhea [13] suggesting a link between the diarrheagenic and apoptotic pathways stimulated by STb. Indeed, studies conducted on Clostridium perfringens enterotoxin revealed that this toxin is capable of increasing intracellular calcium levels during both diarrhea [43] and apoptosis [44] and of inducing histological damages to the intestine [43] similar to the ones observed for STb [20].…”

“…STb is then internalized by cells resulting in the stimulation of a pertussis toxin-sensitive GTP-binding regulatory protein [13]. This causes an influx of extracellular calcium ions [13] through a receptor-dependent ligand-gated calcium channel activating calmodulin-dependent kinase II [14].…”

“…This causes an influx of extracellular calcium ions [13] through a receptor-dependent ligand-gated calcium channel activating calmodulin-dependent kinase II [14]. The increased calcium level is believed to stimulate the activities of phospholipases and water from enterocytes resulting in watery diarrhea [15][16][17].…”

Les récepteurs des entérotoxines bactériennes

“…Le calcium intracellulaire active le métabolisme de l'acide arachidonique pour la synthèse de la prostaglandine E2 (PGE2) [46], mais la voie principale serait celle de la calmoduline [47]. Les différentes étapes seraient les suivantes : 1) la toxine STb se fixe à un récep-teur membranaire, le sulfatide [125,126] qui activerait une protéine G, stimulant l'ouverture d'un canal et l'entrée du Ca 2+ extracellulaire dans la cellule [31], 2) le Ca 2+ intracellulaire active la calmoduline, une protéine complexant le Ca 2+ , qui à son tour active la kinase II dépendante de la calmoduline [47], 3) la kinase II activée va probablement catalyser la phosphorylation de certaines protéines, telles que des protéines membranaires de transport des ions (pour illustration voir [33]). …”

Escherichia coli heat-stable enterotoxin b (STb) in vivo internalization within rat intestinal epithelial cells

“…In vitro studies have shown that the intestinal secretion pathway involves the activation of a GTP-binding regulatory protein (G α i3 protein) sensitive to pertussis toxin. This action results in an intracellular calcium elevation through a receptor-dependent ligand-gated Ca 2+ channel [3]. The ensuing high level of intracellular Ca 2+ is presumably involved in activation of a calmodulin-dependent protein kinase II (CaMK II) which could open an undetermined ionic channel [8].…”