Comparison of the Action of Escherichia coli Enterotoxin on the Thymocyte Adenylate Cyclase-Cyclic Adenosine Monophosphate System to That of Cholera Toxin and Prostaglandin E ₁

Abstract

Mouse thymocytes were used to compare mechanisms by which Vibrio cholerae and heat-labile Escherichia coli enterotoxins activate the adenylate cyclase-cyclic adenosine monophosphate (AMP) system. Both enterotoxins had their time-delayed increase in cyclic AMP neutralized by antisera to V. cholerae or E. coli enterotoxin, blocked by low concentrations of ganglioside GMI, and destroyed by prior heating. Enterotoxin activation of adenylate cyclase was

Immunological Interrelationships Between Cholera Toxin and the Heat-Labile and Heat-Stable Enterotoxins of Coliform Bacteria

“…Previous investigations have documented the fact that immunological cross-reactivity exists between CT and E. coli LT. Antiserum raised against either of these toxins has been shown to protect against the action of the heterologous toxin, although usually in a less potent manner than against the homologous toxin, when this is assayed by the skin permeability factor (8,22), in vitro tests based on the stimulation of adenyl cyclase (2,14,54), and fluid accumulation in the ligated ileal loop (20,22). This relationship was demonstrated in the present study when the effect of specific antisera on the capacity of these two toxins to induce water secretion was directly assayed.…”

“…Attention is currently being focused on the antigenicity of E. coli enterotoxins with a view toward the possible prophylactic value of immunization against their secretory action (12,44). Although the low-molecular-weight ST form of E. coli toxin has not been found to be antigenic (9,18,49), antisera to the high-molecular-weight LT toxin fraction affords protection against the action of this toxin in evoking fluid in ligated ileal loops (20,22,43,49), in inducing diarrhea in rabbits (48) and gnotobiotic pigs (31), in stimulating adenyl cyclase as tested by various assay systems (5,14,54), and in manifestations of the permeability factor (8,22). In addition, immunological cross-reactivity between E. coli LT and cholera toxin (CT) has been observed in immunodiffusion studies (19), and antisera against either toxin neutralizes the various actions of both the homologous and heterologous antigen (2,8,22,48,54).…”

Mechanism of action of choleragen

“…G M~ can precipitate toxin from solution [51,59,60,811, can interfere with choleragen action [48, 50-53, 55, 60-63,65,71,81,82,89], can block the binding of '251-choleragen [47,76,88] and when immobilized on Agarose beads [49] or as a ganglioside-cerebroside complex [27], can bind choleragen. In several instances, it has been shown that GMl is much more effective than other gangliosides which differ only in the structure of the oligosaccharide moiety [47,51,52,62,83]. Indeed, although it has a lower affinity for choleragen than does the ganglioside, the oligosaccharide of GMl will bind to the toxin and inhibit its precipitation by G M~ [59,60,81,90].…”

“…Certain strains of Escherichia coli elaborate two enterotoxins that may be involved in the pathogenesis of "traveler's diarrhea" [217-2221. One of these, a high-molecularweight [223-2251, heat-labile toxin [62,218,224,, resembles choleragen in its mechanism of action [62,224, (Table VI) and probably exerts its effects by increasing intracellular cyclic AMP [62,233-235; for review, see 5,12,20,236,2371. The E coli enterotoxin has not been purified to homogeneity; it appears, however, to exist in both high-molecular-weight (2 X 1 06) and low-molecular-weight (20,000) species [223][224][225].…”

“…The E coli enterotoxin has not been purified to homogeneity; it appears, however, to exist in both high-molecular-weight (2 X 1 06) and low-molecular-weight (20,000) species [223][224][225]. While thus differing from choleragen, the E coli enterotoxin does have immunologic cross-reactivity [62,224,227,235,238,, probably with the B or ganglioside-binding subunit of choleragen [241,243] . There is some evidence that the E coli enterotoxin will interact with gangliosides [62,63,71,235,246].…”