Modulation of enterotoxin binding and function in vitro and in vivo.
The use of the nontoxic B subunits of cholera and Escherichia coli enterotoxins in vitro and in vivo led to a decrease in toxin binding to target cells and a decrease in toxin-induced effects (i.e., morphological effects, adenylate cyclase activation, and fluid secretion). The reduction in toxin binding involves a process of down-regulation of cellular receptors for the toxin and not toxin occupancy of receptors. The extent of inhibition was dependent on the amount of B subunit used and on the duration of time after its use. Thus, in vivo exposure to a single bolus of B subunit was sufficient to block toxin binding and activity for up to 18 h. Because the B subunit binds extensively to the esophagus and the stomach, peroral administration will require a preparation that allows the subunit to reach the small bowel in a protected form. Our data provide a rationale for using B subunit therapy for short-term protection against the effects of enterotoxins, before the development of an immune response.
Donta
S T
ST
Department of Medicine, University of Connecticut, Newington.
Damiano-Burbach
P
P
Poindexter
N J
NJ
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism* / Q000633:toxicity; D002460:Cell Line; D002772:Cholera Toxin / Q000378:metabolism* / Q000633:toxicity; D004768:Enterotoxins / Q000378:metabolism* / Q000633:toxicity; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D005677:G(M1) Ganglioside; D006162:Guanylate Cyclase; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D011971:Receptors, Immunologic / Q000378:metabolism*; D018000:Receptors, Peptide
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C023552:choleragen receptor; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled