Involvement of 5-Hydroxytryptamine, Prostaglandin E2, and Cyclic Adenosine Monophosphate in Cholera Toxin-Induced Fluid Secretion in the Small Intestine of the Rat In Vivo

Beubler, Eckhard; Kollar, G; Saria, Alois; Bukhave, Klaus; Rask-Madsen, J

doi:10.1016/0016-5085(89)91560-6

Cited by 150 publications

(106 citation statements)

References 43 publications

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“…Another effect of KET than antagonizing 5-HT receptors is its blocking property of the luminal secretion of prostaglandin E2 [2]. In this way, some protective mechanisms of the mucosa, such as the potent anti-inflammatory effect of PGE2 on cells of the mononuclear-phagocytic system in the lamina propria, might be blocked by unspecific effects of 5-HT antagonists.…”

Section: Discussionmentioning

confidence: 99%

“…Mediators in the subepithelial tissues seem to play an important part in the action of CT when causing severe diarrhoea. 5-Hydroxytryptamine (5-HT) and prostaglandin E2 are thought to be major factors in diarrhoea induced by bacterial toxins in the rat and human intestine [2,3]. The involvement of 5-HT in CT-induced intestinal fluid secretion was first suggested by Osaka et al andNilsson et al in 1975 and1983 [4,5].…”

Section: Introductionmentioning

confidence: 99%

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Effect of 5‐hydroxytryptamine antagonists on cholera toxin‐induced secretion in the human jejunum

Eherer

Hinterleitner

Petritsch

et al. 1994

Eur J Clin Investigation

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Abstract. In rats, the combined administration of the 5-HT2 antagonist ketanserin and the 5-HT3 antagonist tropisetron inhibits cholera toxin-induced intestinal secretion. We investigated whether these agents and the 5-HT3 antagonist ondansetron can inhibit cholera toxin-induced secretion in the human jejunum using a segmental perfusion technique. In a first control period the subjects' jejunums were perfused continuously with a plasma-like electrolyte solution. In a second control period they either received a combination of tropisetron plus ketanserin, or tropisetron or ondansetron alone. Cholera toxin 6.25 pg was then administered intrajejunally and the experiments were continued for 4 h. Net water movements during the 4th hour after CT administration minus net water movement during the first control period was used for further calculation and was referred to as net luminal gain. In perfusion studies with tropisetron plus ketanserin resp. ondansetron the net luminal gain of water (+I61 f 26 resp. 189 f 28 ml 30 cm-' h-', mean f SEM) was significantly higher compared to perfusion studies with cholera toxin alone (+94 & 30). Treatment with tropisetron did not change the CT-induced net luminal gain of water (+I08 f 41). Movements of sodium, chloride, bicarbonate and potassium paralleled the movement of water. In agreement with these observations we found a deterioration of clinical parameters after the end of the perfusion studies in four of five subjects treated with CT 25 pg plus ketanserin and tropisetron. Contrary to what has been observed in animal experiments the results in humans indicate enhancement rather than inhibition of CT-induced secretion by administration of 5-HT antagonists. Our results do not support the contention that the intravenous administration of ketanserin, tropisetron or ondansetron might be of potential therapeutic value in patients with Asiatic cholera.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of 5‐hydroxytryptamine antagonists on cholera toxin‐induced secretion in the human jejunum

Eherer

Hinterleitner

Petritsch

et al. 1994

Eur J Clin Investigation

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“…Beubler et al that intraluminal 5-HT levels re¯ect enterochroman cell activity (Beubler & Horina, 1990;Beubler et al, 1989). By contrast, Gershon et al (1990) found high resting levels of 5-HT release with no additional increase detected after cholera toxin exposure.…”

Section: Autoregulation Of Cholera Toxin Induced 5-ht Releasementioning

confidence: 99%

“…Since 5-HT 3 receptors are cation gated ligands, located predominantly on neurones, we also assessed the eect of the local anaesthetic, lidocaine, on cholera toxin-induced 5-HT release and net¯uid secretion (Richardson & Engel, 1986). Preliminary experiments were performed to con®rm that 5-HT levels in the luminal¯uid accurately re¯ect enterochroman cell activity (Beubler & Horina, 1990;Beubler et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

The inhibition of cholera toxin‐induced 5‐HT release by the 5‐HT₃ receptor antagonist, granisetron, in the rat

Turvill¹,

Connor²,

Farthing³

2000

British J Pharmacology

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1 The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the pathophysiology of cholera. 5-HT released from enterochroman cells after cholera toxin exposure is thought to activate nonneuronally (5-HT 2 dependent) and neuronally (5-HT 3 dependent) mediated water and electrolyte secretion. CT-secretion can be reduced by preventing the release of 5-HT. 2 Enterochroman cells possess numerous receptors that, under basal conditions, modulate 5-HT release. These include basolateral 5-HT 3 receptors, the activation of which is known to enhance 5-HT release.3 Until now, 5-HT 3 receptor antagonists (e.g. granisetron) have been thought to inhibit cholera toxin-induced¯uid secretion by blockading 5-HT 3 receptors on secretory enteric neurones. Instead we postulated that they act by inhibiting cholera toxin-induced enterochroman cell degranulation. 4 Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 mg kg 71 , lidoocaine 6 mg kg 71 or saline, were instilled with a supramaximal dose of cholera toxin or saline. Net¯uid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal¯uid 5-HT levels were determined by HPLC with¯uorimetric detection. 5 Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels re¯ect enterochroman cell activity. 6 Both lidocaine and granisetron inhibited¯uid secretion. However, granisetron alone, and proportionately, reduced 5-HT release. 7 The simultaneous inhibition of 5-HT release and¯uid secretion by granisetron suggests that 5-HT release from enterochroman cells is potentiated by endogenous 5-HT 3 receptors. The accentuated 5-HT release promotes cholera toxin-induced¯uid secretion.

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“…9 Further studies have shown that 5-HT is released into the intestinal lumen during exposure to cholera toxin in rats 10,11 and humans. 12 When it was shown, in the rat, that CT-induced secretion can be markedly reduced by 5-HT 3 blockade with granisetron 13 or combined 5-HT 2 and 5-HT 3 blockade with ketanserin and tropisetron 11,14 it was proposed that 5-HT, released by CT, may induce secretion by interaction at mucosal, nonneuronal 5-HT 2 receptors and at neuronal 5-HT 3 receptors.…”

Section: Introductionmentioning

confidence: 99%

In vivo effects of the 5‐HT₃ antagonist alosetron on basal and cholera toxin‐induced secretion in the human jejunum: a segmental perfusion study

Bearcroft

André

Farthing

1997

Aliment Pharmacol Ther

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Background:5‐hydroxytryptamine type 3 receptor antagonists have been shown to reduce fluid and electrolyte secretion or promote absorption in experimental models of small intestinal secretion. The aim of this study was to compare the effects of a single dose (4 mg) of the 5‐hydroxytryptamine type 3 receptor antagonist alosetron and placebo on jejunal fluid and electrolyte movement in humans under basal conditions (n=7) and following cholera toxin‐induced secretion (n=5) in a randomized, double‐blind, crossover design over two separate study periods.Methods:One hour after oral alosetron or placebo, jejunal intubation was performed. A 30 cm segment of jejunum, isolated by two occluding balloons, was exposed to 15 μg of purified cholera toxin for 2 h prior to triple lumen perfusion with a plasma electrolyte solution containing []> 14C]‐polyethylene glycol as a non‐absorbable volume marker. In the basal study, intestinal perfusion was performed without exposure to cholera toxin. Collection and analysis of the effluent from the jejunal segment allowed fluid and electrolyte movement to be calculated.Results:Alosetron treatment increased basal jejunal fluid absorption (median 5.1 mL/cm/h [interquartile range 4.2 to 7.1] compared with placebo (3.8 [3.6 to 4.3] P=0.028, two sided Wilcoxon matched pairs signed rank test)). However, following establishment of a secretory state by cholera toxin, alosetron failed to significantly promote absorption or reduce secretion (0.3 [−1.2 to 1.2] compared to placebo (−4.3 [−7.7 to −1.3] P=0.14)). Adverse events during the study, which included anorexia, nausea, dizziness and loose bowel movements, were not considered to be clinically important. There were no clinically significant changes in laboratory parameters.Conclusion:The 5‐hydroxytyptamine type 3 receptor antagonist, alosetron increased basal fluid absorption in normal human small intestine but failed to have a beneficial effect in cholera toxin‐induced secretion.

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Involvement of 5-Hydroxytryptamine, Prostaglandin E2, and Cyclic Adenosine Monophosphate in Cholera Toxin-Induced Fluid Secretion in the Small Intestine of the Rat In Vivo

Cited by 150 publications

References 43 publications

Effect of 5‐hydroxytryptamine antagonists on cholera toxin‐induced secretion in the human jejunum

Effect of 5‐hydroxytryptamine antagonists on cholera toxin‐induced secretion in the human jejunum

The inhibition of cholera toxin‐induced 5‐HT release by the 5‐HT₃ receptor antagonist, granisetron, in the rat

In vivo effects of the 5‐HT₃ antagonist alosetron on basal and cholera toxin‐induced secretion in the human jejunum: a segmental perfusion study

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Involvement of 5-Hydroxytryptamine, Prostaglandin E2, and Cyclic Adenosine Monophosphate in Cholera Toxin-Induced Fluid Secretion in the Small Intestine of the Rat In Vivo

Cited by 150 publications

References 43 publications

Effect of 5‐hydroxytryptamine antagonists on cholera toxin‐induced secretion in the human jejunum

Effect of 5‐hydroxytryptamine antagonists on cholera toxin‐induced secretion in the human jejunum

The inhibition of cholera toxin‐induced 5‐HT release by the 5‐HT3 receptor antagonist, granisetron, in the rat

In vivo effects of the 5‐HT3 antagonist alosetron on basal and cholera toxin‐induced secretion in the human jejunum: a segmental perfusion study

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The inhibition of cholera toxin‐induced 5‐HT release by the 5‐HT₃ receptor antagonist, granisetron, in the rat

In vivo effects of the 5‐HT₃ antagonist alosetron on basal and cholera toxin‐induced secretion in the human jejunum: a segmental perfusion study