1887

Abstract

SUMMARY

The effects of chlorpromazine (CPZ), berberine and verapamil on intestinal hypersecretion in the rabbit ileal loop model by the heat-labile enterotoxin (LT) of were studied in relation to their ability to inhibit the stimulation ofintestinal adenylate cyclase (AC) by LT. CPZ 5 mg by the intraluminal (i.l.) route and 4 mg/kg bythe intramuscular (i.m.) route significantly reduced LT-induced intestinal hypersecretion. Berberine (10 mg) exerted an inhibitory effect, but only after i.l. administration, whereas verapamil did not exert any significant inhibitory effect when administered eitheri.l.(2.5 mg) or i.m. (4 mg/kg). At concentrations of (0.17-1.34) × 10 CPZ the anti-secretory effect of CPZ correlated with its inhibitory effect on rabbit LT-stimulated intestinal AC. Inhibition of cAMP synthesis was probably not involved in the mechanism of action of the two other substances. These results indicate that CPZ and phenothiazines in general are efficient drugs for reducing LT-induced intestinal hypersecretion and could represent a model for synthesis of new anti-secretory drugs with no tranquiliser side effects.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/00222615-27-2-99
1988-10-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jmm/27/2/medmicro-27-2-99.html?itemId=/content/journal/jmm/10.1099/00222615-27-2-99&mimeType=html&fmt=ahah

References

  1. Abbey D. M., Knoop F. C. 1979; Effect of chlorpromazine on the secretory activity of Escherichia coli heat-stable enterotoxin. Infection and Immunity 26:1000–1003
    [Google Scholar]
  2. Bradford M. M. 1976; A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72:248–254
    [Google Scholar]
  3. Donowitz M., Asarkof N. 1982; Calcium dependence of basal electrolyte transport in rabbit ileum. American Journal of Physiology 243:G28–G35
    [Google Scholar]
  4. Donowitz M. 1983; Ca+ + in the control of active intestinal Na and Cl transport: involvement in neurohumoral action. American Journal of Physiology 245:G165–G177
    [Google Scholar]
  5. Donowitz M., Wicks J., Sharp G. W. G. 1986; Drug therapy for diarreal diseases: a look ahead. Review of Infectious Diseases 8: Suppl 2S188–S201
    [Google Scholar]
  6. Gilman A. G. 1970; A protein binding assay for adenosine 3′: 5′-cyclic monophosphate. Proceedings of the National Academy of Sciences of the USA 67:305–312
    [Google Scholar]
  7. Grasser-Regallet F., Scheftel J. M., Monteil H. 1986; Isolation of a heat-labile enterotoxin produced by a human strain of Escherichia coli by wheat-germ agglutinin affinity chromatography. FEMS Microbiology Letters 35:239–243
    [Google Scholar]
  8. Holmgren J., Lange S., Lonnroth L. 1978; Reversal of cyclic AMP-mediated intestinal secretion in mice by chlorpromazine. Gastroenterology 75:1103–1108
    [Google Scholar]
  9. Ilundain A., Naftalin R. J. 1979; Role of Ca2 + dependent regulator protein in intestinal secretion. Nature 279:446–448
    [Google Scholar]
  10. Jennische E., Lónnroth L. 1982; Effects of chlorpromazine on fluid transport across the intestinal mucosa of the rat. Acta Pharmacologicaet Toxicological305–309
    [Google Scholar]
  11. Larsen J. J. 1982; A study on inhibition of cholera toxin-induced intestinal hypersecretion by neuroleptics. Acta Pharmacologica et Toxicological294–299
    [Google Scholar]
  12. Lónnroth L., Holmgren J., Lange S. 1977; Chlorpromazine inhibits cholera toxin-induced intestinal hypersecretion. Medical Biology (Helsinki) 55:126–129
    [Google Scholar]
  13. Lónnroth I., Andren B., Lange S., Martinsson K., Holmgren J. 1979; Chlorpromazine reverses diarrhea in piglets caused by enteroxigenic Escherichia coli. Infection and Immunity 24:900–905
    [Google Scholar]
  14. Pierce N. F., Wallace C. K. 1972; Stimulation of jejunal secretion by a crude Escherichia coli enterotoxin. Gastroenterology 63:439–448
    [Google Scholar]
  15. Rabbani G. H., Greenough W. B., Holmgren J., Kirkwood B. 1982; Controlled trial of chlorpromazine as antisecretory agent in patients with cholera hydrated intravenously. British Medical Journal 284:1361–1364
    [Google Scholar]
  16. Rabbani G. H., Buttler T., Knight J., Sanyal S. C., Alam K. 1987; Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae. Journal of Infectious Diseases 155:979–984
    [Google Scholar]
  17. Sack R. B., Froehlich J. L. 1982; Berberine inhibits intestinal secretory response of Vibrio cholerae and Escherichia coli enterotpxins. Infection and Immunity 35:471–475
    [Google Scholar]
  18. Scheftel J. C., Martin C., Bober C., Monteil H. 1980; Isolation of an enterotoxic factor elaborated by human enteropathogenic Escherichia coli. FEMS Microbiology Letters 9:125–130
    [Google Scholar]
  19. Smith P. L., Field M. 1980; In vitro antisecretory effects of trifluoperazine and other neuroleptics in rabbit and human small intestine. Gastroenterology 78:1545–1553
    [Google Scholar]
  20. Stern B. K. 1966; Some biochemical properties of suspensions of intestinal epithelial cells. Gastroenterology 51:855–867
    [Google Scholar]
  21. Tai Y. H., Feser J. F., Marnane W. G., Desjeux J. F. 1981; Antisecretory effects of berberine in rat ileum. American Journal of Physiology 241:G253–G258
    [Google Scholar]
  22. Wolff J., Jones A. B. 1970; Inhibition of hormone-sensitive adenyl cyclase by phenothiazines. Proceedings of the National Academy of Sciences of the USA 65:454–459
    [Google Scholar]
  23. Zinner M. J., McFadden D., Sherlock D., Jaffe B. M. 1986; Verapamil reversal of serotonin-induced jejunal secretion of water and electrolytes in awake dogs. Gastroenterology 90:515–519
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/00222615-27-2-99
Loading
/content/journal/jmm/10.1099/00222615-27-2-99
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error