• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of iaiPermissionsJournals.ASM.orgJournalIAI ArticleJournal InfoAuthorsReviewers
Infect Immun. Jul 1983; 41(1): 174–180.
PMCID: PMC264759

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


We examined the effects of disulfide and thiol compounds on Escherichia coli heat-stable enterotoxin (ST) and cyclic GMP-induced secretion. Both cystamine and cystine (disulfide compounds) reduced the secretory responses to submaximal doses of ST in suckling mice (at 0.5 mumol per mouse) and reduced ST activation of guanylate cyclase (by 33 to 73% at 1 mM). In higher doses, cystamine completely eradicated a maximally effective ST dose as well. In addition, the sulfhydryl (thiol) compounds cysteamine, cysteine, and acetylcysteine strikingly reduced the secretory response and the guanylate cyclase response to ST. Neither the disulfide nor the thiol compounds tested reduced cyclic GMP-induced secretion. These studies suggest that disulfide and thiol compounds both block ST-induced secretion before its activation of guanylate cyclase. Taken with the work of others, these findings suggest that disulfide compounds may alter the oxidation reduction state of a cell or act directly on the guanylate cyclase enzyme, whereas thiol compounds may inactivate ST itself by breaking its disulfide bridges, or it may alter guanylate cyclase activation by ST. Both families of compounds deserve further consideration among potential antisecretory agents for application in the control of ST-induced diarrhea.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alderete JF, Robertson DC. Purification and chemical characterization of the heat-stable enterotoxin produced by porcine strains of enterotoxigenic Escherichia coli. Infect Immun. 1978 Mar;19(3):1021–1030. [PMC free article] [PubMed]
  • Ameer B, Greenblatt DJ. Acetaminophen. Ann Intern Med. 1977 Aug;87(2):202–209. [PubMed]
  • Apffel CA, Walker JE, Issarescu S. Tumor rejection in experimental animals treated with radioprotective thiols. Cancer Res. 1975 Feb;35(2):429–437. [PubMed]
  • Brandwein HJ, Lewicki JA, Murad F. Reversible inactivation of guanylate cyclase by mixed disulfide formation. J Biol Chem. 1981 Mar 25;256(6):2958–2962. [PubMed]
  • Burgess MN, Bywater RJ, Cowley CM, Mullan NA, Newsome PM. Biological evaluation of a methanol-soluble, heat-stable Escherichia coli enterotoxin in infant mice, pigs, rabbits, and calves. Infect Immun. 1978 Aug;21(2):526–531. [PMC free article] [PubMed]
  • Chen LC, Rohde JE, Sharp GW. Intestinal adenyl-cyclase activity in human cholera. Lancet. 1971 May 8;1(7706):939–941. [PubMed]
  • Craven PA, DeRubertis FR. Inhibition by retinol and butylated hydroxyanisole of carcinogen-mediated increases in guanylate cyclase activity and guanosine 3':5'-monophosphate accumulation. Cancer Res. 1977 Nov;37(11):4088–4097. [PubMed]
  • Dean AG, Ching YC, Williams RG, Harden LB. Test for Escherichia coli enterotoxin using infant mice: application in a study of diarrhea in children in Honolulu. J Infect Dis. 1972 Apr;125(4):407–411. [PubMed]
  • de Ferreyra EC, de Fenos OM, Bernacchi AS, de Castro CR, Castro JA. Therapeutic effectiveness of cystamine and cysteine to reduce liver cell necrosis induced by several hepatotoxins. Toxicol Appl Pharmacol. 1979 Apr;48(2):221–228. [PubMed]
  • Evans DJ, Jr, Chen LC, Curlin GT, Evans DG. Stimulation of adenyl cyclase by Escherichia coli enterotoxin. Nat New Biol. 1972 Apr 5;236(66):137–138. [PubMed]
  • Field M. Modes of action of enterotoxins from Vibrio cholerae and EScherichia coli. Rev Infect Dis. 1979 Nov-Dec;1(6):918–926. [PubMed]
  • Field M, Graf LH, Jr, Laird WJ, Smith PL. Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2800–2804. [PMC free article] [PubMed]
  • Frantz JC, Robertson DC. Immunological properties of Escherichia coli heat-stable enterotoxins: development of a radioimmunoassay specific for heat-stable enterotoxins with suckling mouse activity. Infect Immun. 1981 Jul;33(1):193–198. [PMC free article] [PubMed]
  • Giannella RA. Suckling mouse model for detection of heat-stable Escherichia coli enterotoxin: characteristics of the model. Infect Immun. 1976 Jul;14(1):95–99. [PMC free article] [PubMed]
  • Greenberg RN, Guerrant RL. E. coli heat-stable enterotoxin. Pharmacol Ther. 1981;13(3):507–531. [PubMed]
  • Greenberg RN, Guerrant RL, Chang B, Robertson DC, Murad F. Inhibition of Escherichia coli heat-stable enterotoxin effects on intestinal guanylate cyclase and fluid secretion by quinacrine. Biochem Pharmacol. 1982 Jun 1;31(11):2005–2009. [PubMed]
  • Greenberg RN, Murad F, Chang B, Robertson DC, Guerrant RL. Inhibition of Escherichia coli heat-stable enterotoxin by indomethacin and chlorpromazine. Infect Immun. 1980 Sep;29(3):908–913. [PMC free article] [PubMed]
  • Greenberg RN, Murad F, Guerrant RL. Lanthanum chloride inhibition of the secretory response to Escherichia coli heat-stable enterotoxin. Infect Immun. 1982 Feb;35(2):483–488. [PMC free article] [PubMed]
  • Guerrant RL, Chen LC, Sharp GW. Intestinal adenyl-cyclase activity in canine cholera: correlation with fluid accumulation. J Infect Dis. 1972 Apr;125(4):377–381. [PubMed]
  • Guerrant RL, Ganguly U, Casper AG, Moore EJ, Pierce NF, Carpenter CC. Effect of Escherichia coli on fluid transport across canine small bowel. Mechanism and time-course with enterotoxin and whole bacterial cells. J Clin Invest. 1973 Jul;52(7):1707–1714. [PMC free article] [PubMed]
  • Guerrant RL, Hughes JM, Chang B, Robertson DC, Murad F. Activation of intestinal guanylate cyclase by heat-stable enterotoxin of Escherichia coli: studies of tissue specificity, potential receptors, and intermediates. J Infect Dis. 1980 Aug;142(2):220–228. [PubMed]
  • Gyles CL. Limitations of the infant mouse test for Escherichia coli heat stable enterotoxin. Can J Comp Med. 1979 Oct;43(4):371–379. [PMC free article] [PubMed]
  • Harper JF, Brooker G. Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0 acetylation by acetic anhydride in aqueous solution. J Cyclic Nucleotide Res. 1975;1(4):207–218. [PubMed]
  • Hughes JM, Murad F, Chang B, Guerrant RL. Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli. Nature. 1978 Feb 23;271(5647):755–756. [PubMed]
  • Hughes RD, Gazzard BG, Hanid MA, Trewby PN, Murray-Lyon IM, Davis M, Williams R, Bennet JR. Controlled trial of cysteamine and dimercaprol after paracetamol overdose. Br Med J. 1977 Nov 26;2(6099):1395–1395. [PMC free article] [PubMed]
  • Kapitany RA, Scoot A, Forsyth GW, McKenzie SL, Worthington RW. Evidence for two heat-stable enterotoxins produced by enterotoxigenic Escherichia coli. Infect Immun. 1979 Jun;24(3):965–966. [PMC free article] [PubMed]
  • Katsuki S, Arnold W, Mittal C, Murad F. Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. J Cyclic Nucleotide Res. 1977 Feb;3(1):23–35. [PubMed]
  • Kimura H, Mittal CK, Murad F. Activation of guanylate cyclase from rat liver and other tissues by sodium azide. J Biol Chem. 1975 Oct 25;250(20):8016–8022. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Mittal CK, Murad F. Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: a physiological regulator of guanosine 3',5'-monophosphate formation. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4360–4364. [PMC free article] [PubMed]
  • Murad F, Arnold WP, Mittal CK, Braughler JM. Properties and regulation of guanylate cyclase and some proposed functions for cyclic GMP. Adv Cyclic Nucleotide Res. 1979;11:175–204. [PubMed]
  • Pomerantseva MD, Viklina GA. Vliianie tsistamina na vykhod dominantnykh letal'nykh mutatsii i retsiproknykh translokatsii v polovykh kletkakh myshei, podvergshikhsia gamma-oblucheniiu v raznykh dozakh. Genetika. 1975;10(7):55–61. [PubMed]
  • Prescott LF, Newton RW, Swainson CP, Wright N, Forrest AR, Matthew H. Successful treatment of severe paracetamol overdosage with cysteamine. Lancet. 1974 Apr 6;1(7858):588–592. [PubMed]
  • Solomon AE, Briggs JD, Knepil J, Henry DA, Winchester JF, Birrell R. Therapeutic comparison of thiol compounds in severe paracetamol poisoning. Ann Clin Biochem. 1977 Jul;14(4):200–202. [PubMed]
  • Staples SJ, Asher SE, Giannella RA. Purification and characterization of heat-stable enterotoxin produced by a strain of E. coli pathogenic for man. J Biol Chem. 1980 May 25;255(10):4716–4721. [PubMed]
  • Thoene JG, Oshima RG, Crawhall JC, Olson DL, Schneider JA. Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo. J Clin Invest. 1976 Jul;58(1):180–189. [PMC free article] [PubMed]
  • Vos O, Budke L, Grant GA. In vitro evaluation of some latent radioprotective compounds. Int J Radiat Biol Relat Stud Phys Chem Med. 1976 Nov;30(5):433–448. [PubMed]
  • White AA, Crawford KM, Patt CS, Lad PJ. Activation of soluble guanylate cyclase from rat lung by incubation or by hydrogen peroxide. J Biol Chem. 1976 Dec 10;251(23):7304–7312. [PubMed]
  • Yudkoff M, Foreman JW, Segal S. Effects of cysteamine therapy in nephropathic cystinosis. N Engl J Med. 1981 Jan 15;304(3):141–145. [PubMed]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...