Skip to main content
SpringerLink
Log in

Effects of somatostatin analog SMS 201-995 on enterotoxigenic diarrhea

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Somatostatin analog SMS 201-995 causes a dose-related suppression of the release and/or action of several gastrointestinal hormones and impairs several anterior pituitary functions. Some patients with illness involving abnormal hormonal activity have responded to treatment with SMS 201-995, including resolution of severe secretory diarrhea. This study examined SMS 201-995 inhibition ofEscherichia coli heat-stable enterotoxin STa (STa) effects and effects of the analog in the rabbit RITARD model with enterotoxigenicEscherichia coli. SMS 201-995 did not alter STa binding to its receptor on piglet brush border membranes. The analog, at concentrations of 0.1 μg/ml (0.1 μM) and 1 μg/ml (1 μM) did not significantly alter STa activation of intestinal epithelial cell particulate guanylate cyclase. At maximal dosing the analog significantly reduced intestinal fluid secretion in suckling mice that was induced by either 8-bromo cyclic GMP or STa. In piglets, the analog reduced by 37–44% the amount of diarrhea induced by STa. However, even with maximal dosing, the piglets still had significant diarrhea, although of a lesser amount. In the rabbit RITARD model the drug failed to alter the severe diarrheal response seen when dosing the animals with enterotoxigenicEscherichia coli. Overall, SMS 201-995 had a significant but incomplete effect in reducing the STa effects seen in the various assays. Additionally, in the RITARD model the analog did not alter the clinical responses to various enterotoxigenic bacteria. SMS 201-995 should be useful as a probe into the mechanisms involved in intestinal fluid secretion, but a clinical role in enterotoxigenic gastrointestinal disease was not supported by this study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pless J, Bauer W, Briner U, Doepfner W, Marbach P, Maurer R, Petcher TJ, Reubi J-C, Vonderscher J: Chemistry and pharmacology of SMS 201-995, a long-acting octapeptide analogue of somatostatin. Scand J Gastroenterol 21 (suppl 119):54–64, 1986

    Google Scholar 

  2. Gorden P, Comi R, Maton PN, Go VLW: Somatostatin and somatostatin analogue (SMS 201-995) in the treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med 110:35–50, 1989

    Google Scholar 

  3. Bloom SR, Greenwood C (eds): Proceedings of somatostatin '85: Chemical, physiologic and clinical advances. Scand J Gastroenterol 21 (suppl 119):1986

  4. O'Dorisio TM (ed): Neuroendocrine disorders of the gastroenteropancreatic system: Clinical applications of the somatostatin analogue SMS 201-995. Am J Med 81(suppl 6B):1986

  5. Comi RJ, Gesundheit N, Murray L, Gorden P, Weintraub BD: Response of thyrotropin-secreting pituitary adenomas to a long-acting somatostatin analogue. N Engl J Med 317:12–17, 1987

    Google Scholar 

  6. Ogbonnaya KI, Arem R: Diabetic diarrhea: Pathophysiology, diagnosis, and management. Arch Intern Med 150:262–267, 1990

    Google Scholar 

  7. Dudl RJ, Anderson DS, Forsythe AB, Zeigler MG, O'Dorisio TM: Treatment of diabetic diarrhea and orthostatic hypotension with somatostatin analogue SMS 201-995. Am J Med 83:584–588, 1987

    Google Scholar 

  8. Kvols LK, Buck M, Moertel CG, Schutt AJ, Rubin J, O'Connell MJ, Hahn RG: Treatment of metastatic islet cell carcinoma with a somatostatin analogue (SMS 201-995). Ann Intern Med 107:162–168, 1987

    Google Scholar 

  9. Greenberg RN, Guerrant RL:E. coli heat-stable enterotoxin.In International Encyclopedia of Pharmacology and Therapeutics. F Dorner, J Drews, (eds). Section 119. Oxford, Pergamon Press, 1986, pp 115–151

    Google Scholar 

  10. Saeed AMK, McMillian R, Huckelberry V, Abernathy R, Greenberg RN: Specific receptor forEscherichia coli heat-stable enterotoxin (STa) may determine susceptibility of piglets to diarrheal disease. FEMS Microbiol Lett 43:247–251, 1987

    Google Scholar 

  11. Weisser MM: Intestinal epithelial cell surface membranes glycoprotein synthesis. I. An indicator of cellular differentiation. J Biol Chem 248:2536–2541, 1973

    Google Scholar 

  12. Hauser H, Howell K, Dawson RMC, Bowyer DE: Rabbit small intestinal brush border membrane preparation and lipid composition. Biochim Biophys Acta 602:567–577, 1980

    Google Scholar 

  13. Dahlquist A: Assay of intestinal disaccharidases. Anal Biochem 22:99–107, 1968

    Google Scholar 

  14. Greenberg RN, Saeed AMK: Purification ofEscherichia coli heat-stable enterotoxin. Methods Enzymol 165:126–137, 1988

    Google Scholar 

  15. Greenberg RN, Murad F, Chang B, Robertson DC, Guerrant RL: Inhibition ofEscherichia coli heat-stable enterotoxin by indomethacin and chlorpromazine. Infect Immun 29:908–913, 1980

    Google Scholar 

  16. Harper JF, Brooker G: Femtomole sensitivity radioimmunoassay for cyclic AMP and cyclic GMP after 2′-O-acetylation by acetic anhydride in aqueous solution. J Cyclic Nucleotide Res 1:207–218, 1975

    Google Scholar 

  17. Saeed AMK, Greenberg RN: Preparative purification ofEscherichia coli heat-stable enterotoxin. Anal Biochem 151:431–437, 1985

    Google Scholar 

  18. Spira WM, Sack RB, Froehlich JL: Simple adult rabbit model forVibrio cholerae and enterotoxigenicEscherichia coli diarrhea. Infect Immun 32:739–747, 1981

    Google Scholar 

  19. Saeed AMK, Magnuson N, Gay CC, Greenberg RN: Characterization of heat-stable enterotoxin from a hypertoxigenicEscherichia coli strain that is pathogenic for cattle. Infect Immun 53:445–447, 1986

    Google Scholar 

  20. Yoshioka M, Asakura H, Hamada Y, Miura S, Kobayashi K, Morishita T, Morita A, Tsuchiya M: Inhibitory effect of somatostatin on cholera toxin-induced diarrhea and glycoenzyme secretion in the rat intestine. Digestion 36:141–147, 1987

    Google Scholar 

  21. Fedorak RN, Kotake A, Douglas F, Chang EB: Inhibition of cholera toxin-stimulated intestinal secretion by CGS 9343B in rats: A specific calmodulin inhibitor. J Pediatr Gastroenterol Nutr 8:252–258, 1989

    Google Scholar 

  22. Cooper JC, Williams NS, King RFGJ, Barker MCJ: Effects of a long-acting somatostatin analogue in patients with severe ileostomy diarrhoea. Br J Surg 73:128–131, 1986

    Google Scholar 

  23. Fedorak RN, Allen SL: Effect of somatostatin analog (SMS 201-995) on thein vivo intestinal fluid transport in rats: A limited systemic effect. Dig Dis Sci 34:567–572, 1989

    Google Scholar 

  24. Fassler JE, O'Dorisio TM, Mekhjian HS, Gaginella TS: Octreotide inhibits increases in short-circuit current induced in rat colon by VIP, substance P, serotonin and aminophylline. Regul Pept 29:189–197, 1990

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Veterans Administration Medical Center, 63125, St. Louis, Missouri

    Richard N. Greenberg MD

Authors
  1. Richard N. Greenberg MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported by the Ralston Purina Co., St. Louis, Missouri, by Sandoz Inc., East Hanover, New Jersey, and by the Department of Veterans Affairs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Greenberg, R.N. Effects of somatostatin analog SMS 201-995 on enterotoxigenic diarrhea. Digest Dis Sci 36, 1768–1773 (1991). https://doi.org/10.1007/BF01296623

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01296623

Key Words

Search

Navigation