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  • 1
    ISSN: 1432-1912
    Keywords: Enterochromaffin cells ; 5-Hydroxytryptamine ; Guinea-pig intestine ; Acetylcholine ; Cisplatin ; 5-HT3 receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated segments of the guinea-pig small intestine were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent determined by high pressure liquid chromatography with electrochemical detection. Release of acetylcholine from isolated superfused intestinal segments was determined as outflow of [3H]radioactivity from preparations preincubated with [3H]choline. Cisplatin (3 μM) increased the outflow of 5-HT and 5-HIAA by about 90%. At 30 and 100 μM cisplatin decreased the outflow of 5-HT and its metabolite by 40%–50%. The stimulatory effect of cisplatin was consistently observed only when the bicarbonate-phosphate buffer of the Tyrode's solution was replaced by HEPES-buffer. The stimulatory effect of cisplatin was abolished in the absence of extracellular calcium or presence of tetrodotoxin (1 μM). The stimulatory effect of cisplatin was also prevented by hexamethonium (100 μM) or scopolamine (100 nM). The 5-HT3 receptor antagonists ondansetron and ICS 205-930 in concentrations as low as 1 pM also abolished the stimulatory effect of cisplatin. The 5-HT3 receptor antagonist MDL 72222 prevented the stimulatory effect of cisplatin only at a concentration of 1 μM. None of the 5-HT3 receptor antagonists alone significantly altered the outflow of 5-HT and 5-HIAA. Cisplatin (3 μM) enhanced the outflow of [3H]radioactivity from intestinal segments and caused longitudinal muscle contractions that were abolished by 100 nM scopolamine. In conclusion, cisplatin, at concentrations which occur during anti-cancer therapy in humans and induce emesis, increases the release of 5-HT from the enterochromaffin cells of the small intestine of the guinea-pig. This effect of cisplatin is mediated by a cascade of events which involves release of acetylcholine and stimulation of 5-HT3 receptors.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 347 (1993), S. 137-140 
    ISSN: 1432-1912
    Keywords: Enterochromaffin cells ; 5-Hydroxytryptamine release ; 5-HT3 receptors ; 5-HT4 receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of agonists and antagonists of 5-hydroxytryptamine (5-HT) receptors on the release of endogenous 5-HT from enterochromaffin cells were studied in the vascularly perfused isolated guinea-pig small intestine. The experiments were done in the presence of tetrodotoxin in order to exclude a neuronally mediated influence on 5-HT release. The 5-HT3 receptor agonist 2-methyl-5-HT increased 5-HT release, and this effect was antagonized by 1 nmol/l tropisetron. Nanomolar concentrations of tropisetron, MDL 72 222 and granisetron decreased 5-HT release. Ondansetron (0.1 and 1 μmol/1) did not modify 5-HT release. 5-Methoxytryptamine, BIMU8 and cisapride concentration-dependently inhibited 5-HT release. BIMU8 was more potent than 5-methoxytryptamine. Micromolar concentrations of tropisetron (1 and 10 μmol/1) enhanced the release, whilst methiothepine (0.1 μmol/l) did not affect the release of 5-HT. The results suggest that enterochromaffin cells of the guinea-pig ileum do not contain 5-HT1 and 5-HT2 receptors, but are endowed with 5-HT3 and 5-HT4 autoreceptors. Activation of the 5-HT3 receptors triggers a positive feedback mechanism leading to an increase of 5-HT release. The 5-HT3 receptors on the enterochromaffin cell differ from neuronal 5-HT3 receptors on guinea-pig myenteric plexus by their high affinity for tropisetron and MDL 72 222, and their very low affinity for ondansetron. Stimulation of 5-HT4 receptors causes inhibition of release; the inhibitory 5-HT4 receptor mechanism appears to predominate.
    Type of Medium: Electronic Resource
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