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. 1979 Dec;26(3):1000–1003. doi: 10.1128/iai.26.3.1000-1003.1979

Effect of chlorpromazine on the secretory activity of Escherichia coli heat-stable enterotoxin.

D M Abbey, F C Knoop
PMCID: PMC414718  PMID: 393625

Abstract

The effect of chlorpromazine on the net intestinal accumulation of fluid induced by Escherichia coli heat-stable (ST) enterotoxin in an infant mouse model was examined. Chlorpromazine, when administered with ST enterotoxin, caused a highly significant decrease in net intestinal fluid accumulation. The inhibition of ST activity was dose dependent with various concentrations of chlorpromazine (P less than 0.001). A significant inhibition of toxic activity was also observed when chlorpromazine was administered before (P less than 0.02) or after (P less than 0.05) ST enterotoxin challenge. No significant differences in fluid accumulation were observed between control mice treated with buffer alone and those treated with only chlorpromazine. These data indicate that chlorpromazine markedly decreases the net intestinal fluid accumulation induced by E. coli ST enterotoxin. Further studies on the potential use of chlorpromazine in both the prophylaxis and the treatment of diarrheal diseases appear warranted.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alderete J. F., Robertson D. C. Nutrition and enterotoxin synthesis by enterotoxigenic strains of Escherichia coli: defined medium for production of heat-stable enterotoxin. Infect Immun. 1977 Mar;15(3):781–788. doi: 10.1128/iai.15.3.781-788.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dean A. G., Ching Y. C., Williams R. G., Harden L. B. 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. doi: 10.1093/infdis/125.4.407. [DOI] [PubMed] [Google Scholar]
  3. Evans D. J., Jr, Evans D. G., DuPont H. L., Orskov F., Orskov I. Patterns of loss of enterotoxigenicity by Escherichia coli isolated from adults with diarrhea: suggestive evidence for an interrelationship with serotype. Infect Immun. 1977 Jul;17(1):105–111. doi: 10.1128/iai.17.1.105-111.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Field M., Fromm D., al-Awqati Q., Greenough W. B., 3rd Effect of cholera enterotoxin on ion transport across isolated ileal mucosa. J Clin Invest. 1972 Apr;51(4):796–804. doi: 10.1172/JCI106874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Field M. Mechanisms of action of cholera and Escherichia coli enterotoxins. Am J Clin Nutr. 1979 Jan;32(1):189–196. doi: 10.1093/ajcn/32.1.189. [DOI] [PubMed] [Google Scholar]
  6. Giannella R. A., Drake K. W. Effect of purified Escherichia coli heat-stable enterotoxin on intestinal cyclic nucleotide metabolism and fluid secretion. Infect Immun. 1979 Apr;24(1):19–23. doi: 10.1128/iai.24.1.19-23.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holmgren J., Lange S., Lönnroth I. Reversal of cyclic AMP-mediated intestinal secretion in mice by chlorpromazine. Gastroenterology. 1978 Dec;75(6):1103–1108. [PubMed] [Google Scholar]
  8. Hughes J. M., Murad F., Chang B., Guerrant R. L. Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli. Nature. 1978 Feb 23;271(5647):755–756. doi: 10.1038/271755a0. [DOI] [PubMed] [Google Scholar]
  9. Kakiuchi S., Rall T. W. The influence of chemical agents on the accumulation of adenosine 3',5'-Phosphate in slices of rabbit cerebellum. Mol Pharmacol. 1968 Jul;4(4):367–378. [PubMed] [Google Scholar]
  10. Kimberg D. V., Field M., Johnson J., Henderson A., Gershon E. Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins. J Clin Invest. 1971 Jun;50(6):1218–1230. doi: 10.1172/JCI106599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kimbert D. V. Cyclic nucleotides and their role in gastrointestinal secretion. Gastroenterology. 1974 Nov;67(5):1023–1064. [PubMed] [Google Scholar]
  12. Lönnroth I., Andrén B., Lange S., Martinsson K., Holmgren J. Chlorpromazine reverses diarrhea in piglets caused by enterotoxigenic Escherichia coli. Infect Immun. 1979 Jun;24(3):900–905. doi: 10.1128/iai.24.3.900-905.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lönnroth I., Holmgren J., Lange S. Chlorpromazine inhibits cholera toxin-induced intestinal hypersecretion. Med Biol. 1977 Jun;55(3):126–129. [PubMed] [Google Scholar]
  14. Madsen G. L., Knoop F. C. Inhibition of the secretory activity of Escherichia coli heat-stable enterotoxin by indomethacin. Infect Immun. 1978 Oct;22(1):143–147. doi: 10.1128/iai.22.1.143-147.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Newsome P. M., Burgess M. N., Mullan N. A. Effect of Escherichia coli heat-stable enterotoxin on cyclic GMP levels in mouse intestine. Infect Immun. 1978 Oct;22(1):290–291. doi: 10.1128/iai.22.1.290-291.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Palmer G. C., Robison G. A., Sulser F. Modification by spychotropic drugs of the cyclic adenosine monophosphate response to norepinephrine in rat brain. Biochem Pharmacol. 1971 Jan;20(1):236–239. doi: 10.1016/0006-2952(71)90491-6. [DOI] [PubMed] [Google Scholar]
  17. Parkinson D. K., Ebel H., DiBona D. R., Sharp G. W. Localization of the action of cholera toxin on adenyl cyclase in mucosal epithelial cells of rabbit intestine. J Clin Invest. 1972 Sep;51(9):2292–2298. doi: 10.1172/JCI107039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rabbani G. H., Greenough W. B., 3rd, Holmgren J., Lönnroth I. Chlorpromazine reduces fluid-loss in cholera. Lancet. 1979 Feb 24;1(8113):410–412. doi: 10.1016/s0140-6736(79)90885-7. [DOI] [PubMed] [Google Scholar]
  19. Sack D. A., Merson M. H., Wells J. G., Sack R. B., Morris G. K. Diarrhoea associated with heat-stable enterotoxin-producing strains of Escherichia coli. Lancet. 1975 Aug 9;2(7928):239–241. doi: 10.1016/s0140-6736(75)90958-7. [DOI] [PubMed] [Google Scholar]
  20. Sack R. B., Jacobs B., Mitra R. Antitoxin responses to infections with enterotoxigenic Escherichia coli. J Infect Dis. 1974 Mar;129(3):330–335. doi: 10.1093/infdis/129.3.330. [DOI] [PubMed] [Google Scholar]
  21. Schafer D. E., Lust W. D., Sircar B., Goldberg N. D. Elevated concentration of adenosine 3':5'-cyclic monophosphate in intestinal mucosa after treatment with cholera toxin. Proc Natl Acad Sci U S A. 1970 Oct;67(2):851–856. doi: 10.1073/pnas.67.2.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sharp G. W., Hynie S. Stimulation of intestinal adenyl cyclase by cholera toxin. Nature. 1971 Jan 22;229(5282):266–269. doi: 10.1038/229266a0. [DOI] [PubMed] [Google Scholar]
  23. Wolff J., Jones A. B. Inhibition of hormone-sensitive adenyl cyclase by phenothiazines. Proc Natl Acad Sci U S A. 1970 Feb;65(2):454–459. doi: 10.1073/pnas.65.2.454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. el-Awqati Q., Cameron J. L., Greenough W. B., 3rd Electrolyte transport in human ileum: effect of purified cholera exotoxin. Am J Physiol. 1973 Apr;224(4):818–823. doi: 10.1152/ajplegacy.1973.224.4.818. [DOI] [PubMed] [Google Scholar]

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