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scherichiacoli STbtoxin and prostaglandin iproductionEnterotoxigenic Escherichia coli cause diar-rhoeal disease in humans and animals byelaboration of exotoxins which are divided iinto two groups based on thermal stability.The heat-labile LT) and the heat-stable STaenterotoxins have been investigated in detailand much is known about their mechanismsof action and cellular targets. On the otherhand, studies to determine the mechanism of iaction of E coli STb heat-stable) toxin are istill required to elucidate precisely the way s) iin which it acts on intestinal tissues.

In spite of only rare studies conducted onthe subject, some important facts have begun ito emerge. A first study done by Greenberg iet a f . 2),using heat-treated 65*C,30 min)STb culture filtrates, investigated the centralpathway s) triggered by STb. They were ithe first to observe a stimulation 8-fold) ofthe intestinal secretion of prostaglandin E, iPGE,) in response to the administered toxin.STb had an early onset of action 30min inthe weaned pig loop assay) that resulted inintestinal PGE, secretion. At the same time,it was shown that STb stimulated secretion

through a cyclic-nucleotide-independent Receptor stimulation could be coupled topathway. Thi s early report thus indicated the activation of phosphoinositide turnoverthat STb was acting differently from LT and i and/or activation of phospholipase A,. In theSTa. Surprisingly, these observations were i gut, PGE, and serotonin promote intestinalonly recently confirmed. In fact, Hitotsubashi secretion by apparently independent mecha-et al S), using purified toxin, confirmed nisms, yet the release of serotonin and thethat STb did not alter cyclic GMP nor cyclic i synthesis of PGE, may be coupled events.AMP levels in intestinal mucosal cells. As a i Overall, PGE, formation appears to ariseresult of STb action, the level of PGE, j through both serotonin-dependent andincreased and prostaglandin inhibitors such i serotonin-independent pathways 3) . As weas aspirin and indomethacin significantly know that PGE, abolishes neutral sodiumreduced the response to STb. Reduction of i chloride absorption and increases electro-fluid secretion brought about by cyclo- genic chloride ion secretion, it is quiteoxygenase inhibitors has also been observed puzzling to relate bicarbonate secretion andby us, using the rat loop assay as the animal the absence of chloride observed in an Ussingmodel J. D. Dubreuil A. Letellier, unpub- chamber in response to STb 8).lished observations). From another point of view, being aware

Later, Fujii et af 1)established that che that PGE, has a direct effect on smoothquantity of PGE, produced by intestinal cells muscle cells, its production in response towas directly related to the quantity of toxin i STb could be responsible for the spontaneousadministered to the mouse. Furthermore, the t motility observed in the mouse ileum. Asquantity of PGE, also correlated with the i expected from this implication, papaverine,volume of fluid released into the intestinal i which is known to cause relaxation of smoothlumen. Since then, two other groups have also muscle, had an inhibitory effect on STb 4).reported that PGE, and 5-hydroxytryptamine i In conclusion, although some secretionserotonin), re released into the luminal fluid i mediators have been clearly shown to beas a result of STb action 3, 7) . Peterson produced in response to STb toxin, theWhipp 7), when comparing the secretory intricacy of their role in the product ion ofeffectsof cholera toxin CT),STa and STb in diarrhoea1 disease still demands somethe pig intestinal loop model, observed that additional studies.combining maximal doses of STa and STband of CT and STb yielded additive fluid ; J. Daniel Dubreuilaccumulation. Together these experiments iconfirmed that the mechanism of action of iSTb enterotoxin is distinct from STa and CT, ialthough CT as well as STb stimulated the irelease of PGE, and serotonin.To summarize, results indicate that STbin v vo causes a dose-dependent increase inluminal PGE, and serotonin which are knownsecretagogues. As cyclooxygenase inhibitorsdiminish fluid secretion by STb, stimulationof arachidonic acid metabolism in intestinalepithelial cells is clearly established. O n theother hand, PGE, is known to stimulateintestinal adenylate cyclase, resulting in theformation of CAMP 6 ) .For STb, this rise in icyclic nucleotides that subsequently resultin chloride secretion has not been observed.Thus, serotonin could mediate the remainingsecretory effect observed for STb, In fact, atleast part of PGE, seems to be produced inresponse to serotonin receptor stimulationas ketanserin, a receptor antagonist of sero- itonin, reduced the level of PGE, observed. i

Communications should be in the formof letters and should be brief and to thepoint. A single small Table or Figure maybe included, as may a limited number ofreferences cited in the text by numbers,and listed in alphabetical order at the endof the letter). A short title fewer than 50characters) should be provided.Approval for publication rests withthe Editor-in-Chief, who reserves theright to edit letters and/or to make abrief reply Other interested persons mayalso be invited to reply The Editorsof Microbiology do not necessarilyagree with the views expressed inMicrobiohgy Comment.Contributions should be addressed to theEditor-in-Chief via the Editorial Office.

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Microbiology CommentGroupe de Recherche sur les Maladieslnfectieuses du Porc, DCpartem ent d ePathologie et Micro bio log ie, FacultC deMCdecine VCtbrinaire, UniversitC deMon treal , Saint-Hyacinthe, QuCbec,Canada J2S 7C6Tel: I 450 773 8521 ext. 8433Fax: +1 45 778 8108e-ma I:daniel-dubreu gumontrea I ca1. Fujii, Y, ondo, Y Keinosuke, 0 1995).Involvement of prostaglandin E, synthesis in theintestinal secretory action of Escherichia coli heat-si

enterotoxin 11.F MSMi c~o b i o l ett 130,259-266.2. Greenberg, R.N. Kennedy, D. J., Stephenson, A. H.,Lonigro, A. J., Murad, F Guerrant, R. L. 1981).Stimulation of intestinal prostaglandin secretion by athird type of E. colienterotoxin STb).ClinRes 30,367A.3. Harville, B. A. Dreyfus, L. A. 1995).Involvementof 5-hydroxytryptamine arid prostaglandin E, in theintestinal secretory action of Escherichia coli heat-stableenterotoxin B. Znfect Immun 3,745-750.4. Hitotsubashi, S., Akagi, M., Saitou, A,, Yamanaka, H.,Fujii, Y Okamoto, K. 1992).Action of Escherichiacoli heat-stable enterotoxin I on isolated sections ofmouse ileum.FEMS Microbiol Lett 90,249-252.5.Hitotsubashi, S. Fujii, Y.,Yamanaka, H.table i Okamoto, K. 1992).Some properties of purified

Escherichiacoliheat-stable enterotoxin 11. Infect Immun60,44684474,6. Kimberg, D. V, ield, M., Johnson, J., Henderson, A.Gershon, E. 1971).Stimulation of intestinal mucosaladenyl cyclase by cholera enterotoxin andprostaglandins. lin nvest SO, 1218-1230.7. Peterson, J. W. Whipp, S. C. 1995).Comparisonof the mechanism of action of cholera toxin and the heat-stable enterotoxins of Escherichia col i . Infect Imrnun 63 ,8. Weikel, C. S. Guerrant, R. L. 1985). Tbenterotoxin of Escherichia col i : cyclic nucleotide-independent secretion. In MicrobialToxins andDiarrhoea1 Disease CibaFoundation Symposium 114pp. 94115. Edited by D vered J. Whelan. Lond on:Pitrnan.

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