Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine.

Field, Michael; Graf, Liselotte; Laird, W; Smith, Philip L.

doi:10.1073/pnas.75.6.2800

Cited by 507 publications

(343 citation statements)

References 23 publications

Supporting

Mentioning

324

Contrasting

Unclassified

Order By: Relevance

“…ST peptides bind to a receptor on intestinal cells and activate membrane-bound guanylyl cyclase [7,81. Increased levels of cyclic GMP (cGMP) within the cell are hypothesised to lead to enhanced C1-secretion from the intestinal cell by as yet undefined mechanisms, resulting in fluid loss and subsequent diarrhoea Early biochemical studies had postulated that in rat intestinal membranes the ST-binding and guanylyl cyclase activities were located on separate molecules [lo].…”

mentioning

confidence: 99%

Characterization and partial purification of the human receptor for the heat‐stable enterotoxin

Visweswariah¹,

Ramachandran²,

Ramamohan³

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

The receptor for the Escherichia coli heat-stable enterotoxin has been characterized and partially purified from the T84 human colonic cell line. Using a novel mutant heat-stable enterotoxin peptide as a radioligand (the C-terminal tyrosine residue is replaced by phenylalanine in the mutant), a single class of high-affinity receptor sites was detected in T84 cells, with a Kd of 0.1 nM, similar in affinity to the receptor described in human intestinal tissue. The receptor was solubilised from T84 cell membranes and affinity cross-linking of the solubilised preparation indicated that a single species of M, 160000 served as the receptor. Freshly solubilised preparations of the receptor retained heat-stable enterotoxin-activable guanylyl cyclase activity. Purification of the receptor was achieved through sequential affinity chromatography on GTP-epoxy-Sepharose and wheat-germ-agglutinin columns resulting in purification of the receptor by 3000 fold. The heat-stable enterotoxin-binding characteristics of the receptor were unchanged during the purification and silver staining of the purified receptor preparation indicated a band of M, 160000, which was specifically cross-linked to the lZ51-labeled mutant peptide. The purified receptor retained guanylyl cyclase activity, but the activity was not stimulated on addition of human heat-stable enterotoxin, suggesting that accessory structural factors may be involved in the activation of the guanylyl cyclase/receptor.The heat-stable enterotoxins (ST) are a family of lowmolecular-mass peptide toxins, and are one of the major causes of watery secretory diarrhoea all over the world [1, 21. Various forms of the toxins, differing in amino acid sequence, are produced by a number of pathogenic bacteria [3, 41, and all these peptides contain a cysteine-rich core essential for full biological activity [5, 61. ST peptides bind to a receptor on intestinal cells and activate membrane-bound guanylyl cyclase [7, 81. Increased levels of cyclic GMP (cGMP) within the cell are hypothesised to lead to enhanced C1-secretion from the intestinal cell by as yet undefined mechanisms, resulting in fluid loss and subsequent diarrhoea Early biochemical studies had postulated that in rat intestinal membranes the ST-binding and guanylyl cyclase activities were located on separate molecules [lo]. However, the cloning and expression of the rat and human intestinal ST receptor [ll-131 suggested that the ST receptor was in fact a high-molecular-mass protein and a member of the guanylyl cyclase family of receptors, described earlier for atrial natriuretic factor and the sea urchin egg peptides [14]. These observations implied that the ST-binding and guanylyl cyclase activities were present in the same receptor molecule. How- ever, there is no biochemical evidence using purified receptor preparations to confirm that the ST receptor does in fact exist in the cell as suggested for the recombinant protein. Hugues et al. reported the purification of the rat ST receptor from intestinal membranes using ST-ligand af...

show abstract

mentioning

confidence: 99%

Characterization and partial purification of the human receptor for the heat‐stable enterotoxin

Visweswariah¹,

Ramachandran²,

Ramamohan³

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…Le site de phosphorylation serait la sérine en position 1029 du GC-C pour la PKC [25]. Ainsi, suite à l'attachement de STa, une production de GMPc est déclenchée, qui conduit à l'augmentation de la sécrétion intestinale de chlore et à l'inhibition de l'absorption de sodium [39,42,57,68,118] (pour illustration voir [33]). …”

Section: Activation De La Guanylate Cyclaseunclassified

Les récepteurs des entérotoxines bactériennes

Rousset

2000

Vet. Res.

View full text Add to dashboard Cite

-Bacterial enterotoxin receptors. Enteric bacterial toxins display a great diversity in their structure, molecular weight and mechanism of action. The interaction of enterotoxins with the intestinal mucosa either leads to a direct effect on the cell membrane or an effect on signal transduction within eukaryotic cells. However, before a toxin can affect a cell, it must after its secretion by a microorganism, recognise and bind to a specific surface molecule, its receptor. Membrane receptors of bacterial enterotoxins have been identified as protein, glycoprotein or glycolipid in nature. The chemical nature of the molecules acting as receptors is crucial and during evolution they have been carefully selected. Some toxins, after their interaction with a receptor molecule, will transduce a signal across the cell membrane while remaining at the cell surface. Other toxins, after this initial binding step with a receptor, will be internalised. Others can form pores leading to leakage of cellular components and cell lysis. Receptors that have been identified often comprise a saccharidic chain that is directly involved in the recognition and binding of the toxin. Today, models explaining toxin-receptor interactions are more complex, including multistep events. This review summarises the knowledge of the interactions between bacterial toxins and membrane receptors present on intestinal mucosa. receptor / intestine / enterotoxin / binding epitope / glycosphingolipidRésumé -Les toxines bactériennes entériques présentent une grande diversité autant dans leur structure que dans leur poids moléculaire et leur mécanisme d'action. L'interaction des entérotoxines avec la muqueuse intestinale conduit soit à un effet direct sur la paroi cellulaire de la cellule hôte, soit à un dérèglement des voies de signalisation de celle-ci. Toutefois, avant même d'affecter la cellule cible, la toxine sécrétée par le micro-organisme devra reconnaître et s'attacher à une molécule présente à la surface cellulaire, son récepteur. Les récepteurs membranaires des entérotoxines bactériennes peuvent être de nature protéique, glycoprotéique ou glycolipidique. La nature chimique de ces récepteurs, sur laquelle repose la spécificité, est primordiale et au cours de l'évolution ceuxci ont été soigneusement sélectionnés. Certaines toxines, une fois en contact avec leur récepteur, envoient un signal à l'intérieur de la cellule tout en demeurant à la surface alors que d'autres toxines sont internalisées. Enfin, certaines toxines bactériennes peuvent former des pores dans la membrane Vet. Res. 31 (2000)

show abstract

“…7). This toxin, which stimulates guanylate cyclase (Field, Graf, Laird & Smith, 1978), induced secretion after 60 min incubation of sacs. There was no significant difference in secretion of fluid from sacs treated with 406 REVERSAL OF CHOLERA TOXIN-INDUCED SECRETION E. coli enterotoxin STa with or without 10 mM-nicotinamide.…”

Section: E Coli Sta and Theophylline-induced 8ecretionmentioning

confidence: 99%

Reversal and inhibition of cholera toxin‐induced secretion in isolated rabbit ileum.

Falk¹,

Freeman²,

Marshall³

et al. 1990

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. Cholera toxin (1 jig/ml) abolished net fluid absorption by everted sacs of rabbit ileum, leading to net fluid secretion. This action occurred via the toxin-catalysed ADP ribosylation of the stimulatory GTP-binding protein G. which is linked to adenylate cyclase. Nicotinamide (10 mM), a reaction product of ADP ribosylation, reversed cholera toxin-induced secretion, restoring absorption. Lower concentrations of nicotinamide induced partial reversal.2. Nicotinamide (1 mM) blocked the secretory action of cholera toxin applied to ileal sacs. This inhibitory action was more effective in the presence of methionine (1 mM).3. Other inhibitors of ADP ribosylation, benzamide and adenine, blocked the secretory action of cholera toxin. Hypoxanthine, an analogue and metabolite of adenine, was similarly effective.4. Nicotinamide was not, however, effective in blocking or reversing the secretory action of theophylline (10 mM) or of heat-stable E. coli enterotoxin STa. This indicates that nicotinamide has a highly specific action against ADP ribosylating toxins.5. It is proposed that nicotinamide reverses the secretory action of cholera toxin by reversing ADP ribosylation, simply by the law of mass action. This counters the established idea that the effects of cholera and other ADP-ribosylating toxins are irreversible under physiological conditions.

show abstract

Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine.

Cited by 507 publications

References 23 publications

Characterization and partial purification of the human receptor for the heat‐stable enterotoxin

Characterization and partial purification of the human receptor for the heat‐stable enterotoxin

Les récepteurs des entérotoxines bactériennes

Reversal and inhibition of cholera toxin‐induced secretion in isolated rabbit ileum.

Contact Info

Product

Resources

About