Summary
The secretory effect of cholera toxin on the gut has been ascribed to the activation of submucosal 5-hydroxytryptamine receptors by 5-hydroxytryptamine released from the enterochromaffin cells. The hypothesis that neuronally located 5-HT3 receptors are involved in cholera toxin-induced diarrhoea has now been tested. Intestinal secretion was stimulated in mice by oral administration of pure cholera toxin and the effects of ICS 205-930, a potent and selective antagonist at 5-HT3 receptors, and of ketanserin, a compound that blocks 5-HT2 receptors, were investigated.
Oral administration of cholera toxin resulted in a significant accumulation of fluid in the intestine. Pretreatment of the animals with ICS 205–930 partly prevented this effect and a maximal reduction of about 50% was achieved with doses of 0.3 mg/kg i. p. and higher. Ketanserin had only minimal effects up to a high dose of 1 mg/kg i. p. when a 20% reduction of fluid accumulation was seen. The data support the view that activation of 5-HT3 receptors plays a major role in the secretory effect of cholera toxin in the gut.
References
Anderson JV, Coupe MO, Morris JA, Hodgson HJF, Bloom SR (1987) Remission of symptoms in carcinoid syndrome with a new 5-hydroxytryptamine M receptor antagonist. Br Med J 294:1129
Baird AW, Cuthbert AW (1987) Neuronal involvement in type 1 hypersensitivity reactions in gut epithelia. Br J Pharmacol 92:647–655
Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena PR (1986) Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25:563–576
Cassuto J, Jodal M, Tuttle R, Lundgren O (1981) On the role of intramural nerves in the pathogenesis of cholera toxin-induced intestinal secretion. Scand J Gastroenterol 16:377–384
Fozard JR (1984) MDL 72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn-Schmiedeberg's Arch Pharmacol 326:36–44
Nilsson O, Cassuto J, Larsson PA, Jodal M, Lidberg P, Ahlman H, Dahlström A, Lundgren O (1983) 5-Hydroxytryptamine and cholera secretion: a histochemical and physiological study in cats. Gut 24:542–548
Pierce NF, Greenough WB III, Carpenter CCJ (1971) Vibrio cholerae enterotoxin and its mode of action. Bacteriol Rev 35:1–13
Richardson BP, Engel G (1986) The pharmacology and function of 5-HT3 receptors. Trends Neurosci 9:424–428
Richardson BP, Engel G, Donatsch P, Stadler PA (1985) Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature 316:126–131
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Buchheit, KH. Inhibition of cholera toxin-induced intestinal secretion by the 5-HT3 receptor antagonist ICS 205–930. Naunyn-Schmiedeberg's Arch Pharmacol 339, 704–705 (1989). https://doi.org/10.1007/BF00168665
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DOI: https://doi.org/10.1007/BF00168665