Inhibition of Escherichia coli heat-stable enterotoxin by indomethacin and chlorpromazine.

Infection and Immunity
R N GreenbergR L Guerrant

Abstract

Purified heat-stable enterotoxin (ST) from a procine strain of enterotoxigenic Escherichia coli activates quanylate cyclase in particulate fractions of rat intestinal tissue and induces fluid accumulation in suckling mice. These effects of ST were examined in the presence of either indomethacin or chlorpromazine. We also examined the effects of these two drugs on fluid accumulation in suckling mice induced by the 8-bromo analog of cyclic guanosine monophosphate. Either indomethacin or chlorpromazine reduced ST activation of guanylate cyclase. Both drugs also reduced intestinal fluid accumulation in suckling mice that resulted from submaximal doses of ST (both P < 0.001). However, there was no reduction in fluid secretion by either drug when a maximally effective dose of ST was used, suggesting that inhibition of fluid secretion by both drugs can be overcome by increasing the ST dose and that a threshold level of guanylate cyclase activity results in maximal secretory response. Both drugs also reduced basal guanylate cylase activity in rat intestinal tissue and fluid secreton in suckling mice. Chlorpromazine also reduced intestinal secretion mediated by 8-bromo cyclic guanosine monophosphate (P < 0.001). These findings indicate ...Continue Reading

References

Jun 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·M FieldP L Smith
Feb 24, 1979·Lancet·G H RabbaniI Lönnroth
Jan 1, 1979·Annual Review of Pharmacology and Toxicology·R NickanderA S Ridolfo
Jun 1, 1979·Infection and Immunity·I LönnrothJ Holmgren
May 8, 1971·Lancet·L C ChenG W Sharp
Apr 5, 1972·Nature: New Biology·D J EvansD G Evans
Apr 1, 1972·The Journal of Infectious Diseases·R L GuerrantG W Sharp

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Citations

May 1, 1984·Infection and Immunity·L A DreyfusD C Robertson
Nov 1, 1985·Gastroenterology·G H Rabbani, T Butler
Dec 1, 1991·Digestive Diseases and Sciences·R N Greenberg
Sep 10, 2010·The Journal of Biological Chemistry·Yong ZhouJohn F Hancock

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