Reduction of the secretory response to Escherichia coli heat-stable enterotoxin by thiol and disulfide compounds

Greenberg, Richard N.; Dunn, John A.; Guerrant, Richard L.

doi:10.1128/iai.41.1.174-180.1983

Cited by 28 publications

(17 citation statements)

References 34 publications

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“…Reversal of STa activation of guanylate cyclase. We found, as did Greenberg et al (25), that thiols rapidly destroyed the ability of STa to activate guanylate cyclase. However, destruction was more difficult after the STa had bound to its receptor.…”

Section: Resultssupporting

confidence: 86%

“…These include ot-adrenergic agents (2, 36), anticholinergics (3), berberine (4, 41, 59), morphine andmorphine analogs (2, 56), calmodulin inhibitors (1, 28,40,46), and prostaglandin synthesis inhibitors (27,33). Although some of these may prove to be clinically effective, either alone or in combination (24), we decided to explore the direction taken by Greenberg et al (25), i.e., attempt to interfere with guanylate cyclase activation rather than interrupt the putative sequence of events following cyclic GMP formation. This approach was facilitated by our improvements in the BBMV guanylate cyclase assay, which extended the linear time course of the reaction and resulted in STa-induced activity increases of 40to 50-fold with different preparations of pig BBMV (M. M. R. ElDeib, C. D. Parker, T. L. Veum, G. M. Zinn, and A.…”

Section: Discussionmentioning

confidence: 99%

“…Some of these compounds could apparently reduce STa which was already bound to the membrane receptor and consequently reverse guanylate cyclase activation. The experimental design used by Greenberg et al (25) could not distinguish between inactivation of STa and reversal of activation. Our results raised the possibility that the most effective disulfide reducers could reverse STa-induced secretion, and this hypothesis was examined in a weanling pig bioassay.…”

mentioning

confidence: 99%

“…DeJonge (14) and Rao and Field (37) recently reviewed the evidence supporting the hypothesis that this activation is the initial event leading to intestinal ion secretion. Based on this hypothesis, Greenberg et al examined the effects of disulfide and thiol compounds on STa-induced secretion (25). The disulfide compounds cystamine and cystine, which are capable of reversibly inactivating purified lung guanylate cyclase by mixed disulfide formation (11), decreased STa activation of rat-intestinal-mucosa guanylate cyclase and also the secretory response to STa in suckling mice.…”

mentioning

confidence: 99%

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Reversal of the biological activity of Escherichia coli heat-stable enterotoxin by disulfide-reducing agents

Eldeib¹,

Dove²,

Parker³

et al. 1986

Infect Immun

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Various disulfide-reducing agents, mostly thiols and thiol precursors, were examined for their ability to reduce the disulfide bonds in the Escherichia coli heat-stable enterotoxin STa; reduction of the bonds results in loss of biological activity. The biological activity measured was the stimulation of guanylate cyclase in pig intestinal brush border membranes by STa. Nearly all of the compounds inactivated STa, although at different rates; a smaller number appreciably decreased guanylate cyclase activity when they were introduced into the reaction mixture after STa bound to its receptor. With dithiothreitol, the decrease in reaction rate was both time and concentration dependent and resulted in a reversal to basal activity. The anionic thiols were relatively ineffective in reversing activation, the neutral monothiols were moderately effective, and the aminothiols and neutral dithiols were the most effective. The order of effectiveness of the compounds was S-2-(3aminopropylamino)ethanethiol > 2,3-dimercaptopropanol = 2-aminoethylisothiuronium bromide > dithiothreitol > 2-mercaptoethylamine > ax-thioglycerol. These compounds were used in weanling pig ligatedintestinal-loop bioassays to determine if STa-induced secretion was reduced when they were injected 20 min after the STa. Instead of S-2-(3-aminopropylamino)ethanethiol we used the phosphorylated derivative S-2-(3-aminopropylamino)ethylphosphorothioic acid; this compound and 2,3-dimercaptopropanol were the only compounds that reduced STa-induced secretion and had no direct secretory or pathological effects.The heat-stable enterotoxin STa, which is secreted by pathogenic strains of Escherichia coli, induces secretory diarrhea in humans and animals (26). STa is a family of closely related peptides, each containing 18 or 19 amino acids (5, 7,31,42,48), and is probably synthesized as a 72-residue precursor (35,47). All of the deduced structures have six half-cystine residues in identical postions; a 14amino-acid analog containing the sequence has been synthesized and was even more potent than the natural toxin (6). Reduction of the disulfide linkages destroys biological activity (16,42,48).There is an STa receptor located in the brush border of the intestinal epithelium (20, 23); the brush border is also the location of the majority of mature-enterocyte guanylate cyclase (15,55). Field et al. (18), and later Rao et al. (38) and Guerrant et al. (29), showed that STa activated this brush border membrane guanylate cyclase but not other soluble or particulate guanylate cyclases (29, 38). DeJonge (14) and Rao and Field (37) recently reviewed the evidence supporting the hypothesis that this activation is the initial event leading to intestinal ion secretion. Based on this hypothesis, Greenberg et al. examined the effects of disulfide and thiol compounds on STa-induced secretion (25). The disulfide compounds cystamine and cystine, which are capable of reversibly inactivating purified lung guanylate cyclase by mixed disulfide formation (11), decreased STa activation of r...

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Section: Resultssupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Reversal of the biological activity of Escherichia coli heat-stable enterotoxin by disulfide-reducing agents

Eldeib¹,

Dove²,

Parker³

et al. 1986

Infect Immun

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“…Inhibition of leakage of toxin proteins from the periplasm contrasts with mechanisms of the bactericidal effect proposed by Ikigai et al [109] which involves disruption of the cell membrane, resulting in leakage of molecules essential for the viability of the bacteria. Thiols and disulfide com-pounds reduced the secretion in suckling mice of an enterotoxin produced by E. coli [110].…”

Section: Vero (Shiga) Toxinsmentioning

confidence: 99%

Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas

Friedman¹

2006

Molecular Nutrition Food Res

567

373

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Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.

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Microbial Toxins and Diarrhoeal Diseases: Introduction and Overview

1985

Novartis Foundation Symposia

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Reduction of the secretory response to Escherichia coli heat-stable enterotoxin by thiol and disulfide compounds

Cited by 28 publications

References 34 publications

Reversal of the biological activity of Escherichia coli heat-stable enterotoxin by disulfide-reducing agents

Reversal of the biological activity of Escherichia coli heat-stable enterotoxin by disulfide-reducing agents

Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas

Microbial Toxins and Diarrhoeal Diseases: Introduction and Overview

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