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  • 1
    Electronic Resource
    Electronic Resource
    Temperature-dependent effects of increased intraluminal pressure on serotonin release from the vascularly perfused guinea pig ileum (1987)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 336 (1987), S. 483-486 
    Details
    ISSN: 1432-1912
    Keywords: Serotonin release ; Enterochromaffin cells ; Peristaltic reflex ; Guinea pig ileum ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated segments of the guinea pig ileum were vascularly perfused and the release of endogenous serotonin into the portal effluent was measured. Peristalsis was induced by raising the intraluminal hydrostatic pressure by 500 Pa for 5 min. Serotonin release increased during peristalsis induced by fluid of 37°C, but decreased when the temperature of the intraluminal fluid was between 13°C and 22°C. In the presence of naloxone (0.3 μmol/l) raising the intraluminal pressure with fluid of 37°C caused an inhibition of the serotonin release which was blocked by scopolamine (0.1 μmol/l). Naloxone did not affect the inhibition of Serotonin release during peristalsis caused by fluid of 19°C, neither did indometacin (1 μmol/l). In conclusion, liquid distension of the guinea pig isolated ileum elicits peristaltic activity, and affects the release of serotonin into the portal circulation. The changes in serotonin release depend on the temperature of the fluid passing through the intestinal lumen, whereas peristalsis is not affected by the temperature of the intraluminal fluid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169303
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  • 2
    Electronic Resource
    Electronic Resource
    Cholinergic modulation of the release of 5-hydroxytryptamine from the guinea pig ileum (1987)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 336 (1987), S. 127-132 
    Details
    ISSN: 1432-1912
    Keywords: Enterochromaffin cells ; 5-Hydroxytryptamine ; Guinea pig ileum ; Muscarine receptor ; Nicotine receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated segements of the guinea pig ileum were vascularly perfused and the release of 5-HT and its metabolite 5-HIAA into the portal venous effluent determined by HPLC with electrochemical detection. Test substances were applied via the arterial perfusion medium. Oxotremorine inhibited concentration-dependently the release of 5-HT and 5-HIAA (by 47% at 1 μmol/l). Scopolamine (0.1 μmol/1) did not affect the release of 5-HT and 5-HIAA, but antagonized the effect of oxotremorine. In the presence of TTX (1 μmol/1) oxotremorine (1 pmol/1) increased the release of 5-HT by 150% and that of 5-HIAA by 220%. This increase was completely blocked by scopolamine. Hexamethonium (100 pmol/1) and TTX (1 pmol/1) reduced the release of 5-HT by 32 and 40%, respectively. DMPP (10 pmol/1) increased the release of 5-HT by 57%, and this effect was prevented by hexamethonium. Neither DMPP nor hexamethonium significantly affected the release of 5-HIAA. The enhancing effect of DMPP on 5-HT release was increased and prolonged in the presence of TTX or scopolamine. Nicotine (1, 10 or 30 μmol/l) alone did not cause a consistent increase in the release of 5-HT. However, in the presence of scopolamine nicotine increased the release of 5-HT by 57%. In conclusion, the release of intestinal 5-HT is facilitated via muscarine and nicotine receptors located on the enterochromaffin cells. Indirect evidence suggests that the release of 5-HT is additionally modulated by an as yet unknown inhibitory neurotransmitter released by muscarine receptor activation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00165795
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  • 3
    Electronic Resource
    Electronic Resource
    Cisplatin increases the release of 5-hydroxytryptamine (5-HT) from the isolated vascularly perfused small intestine of the guinea-pig: Involvement of 5-HT3 receptors (1991)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 344 (1991), S. 143-149 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00167211
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  • 4
    Electronic Resource
    Electronic Resource
    NK1- and NK3-receptor mediated inhibition of 5-hydroxytryptamine release from the vascularly perfused small intestine of the guinea-pig (1997)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 689-693 
    Details
    ISSN: 1432-1912
    Keywords: Key words Guinea-pig ileum ; Enterochromaffin cells ; 5-HT release ; Tachykinins ; NK1 receptors ; NK3 receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of tachykinins on the spontaneous release of 5-hydroxytryptamine (5-HT) from the enterochromaffin cells into the portal circulation was investigated in vitro using the vascularly perfused isolated guinea-pig small intestine. 5-HT was determined by HPLC with electrochemical detection. Test substances were applied intraarterially. Substance P (SP) caused a concentration-dependent decrease in 5-HT outflow with an EC50 of 50pmol/l. Similarly, the selective NK1 receptor agonist SP methyl ester (1nmol/l) significantly inhibited 5-HT outflow (to 51±3%). When tetrodotoxin (1μmol/l) was added to the arterial perfusion medium, the inhibition by SP of 5-HT outflow was not affected. The selective NK1 receptor antagonist CP 99994 [(+)-(2S,3S)-3-(2-methoxyben-zylamino)-2-phenylpiperidine] (0.1μmol/l) prevented the inhibitory effect of SP (0.1μmol/l). Neither GR 94800 (PhCO-Ala-Ala-DTrp-Phe-DPro-Pro-NleNH2) (0.1μmol/l) nor SR 142801 [(S)-(N)-(1-(3-(1-benzoyl-3-(3, 4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenyl-piperidin-4-yl)-N-methylacetamide] (10nmol/l), which are selective NK2 and NK3 receptor antagonists, changed the SP-mediated inhibition. The selektive NK3 receptor agonist senktide (10nmol/l) also decreased the 5-HT outflow (to 57±5%). This inhibition was prevented by SR 142801 (10nmol/l) and by tetrodotoxin. CP 99994 (0.1μmol/l) significantly antagonized the senktide-mediated inhibition of 5-HT outflow. The outflow of 5-HT was unaffected when CP 99994, GR 94800 or SR 142801 alone were added to the perfusion medium. It is concluded that the release of 5-HT from enterochromaffin cells is directly inhibited by NK1 receptors, and indirectly by neuronal NK3 receptors whose stimulation leads to the release of SP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005106
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  • 5
    Electronic Resource
    Electronic Resource
    Characterization of the muscarine receptors involved in the modulation of serotonin release from the vascularly perfused small intestine of guinea pig (1989)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 263-267 
    Details
    ISSN: 1432-1912
    Keywords: 5-HT-release ; Enterochromaffin cells ; Muscarine receptor subtypes ; McN-A-343, pilocarpine, oxotremorine, pirenzepine ; Indometacin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated small intestinal segments of the guinea pig were arterially perfused and the release of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent measured by HPLC with electrochemical detection. Test substances were applied via the arterial perfusion medium. McN-A-343, pilocarpine and oxotremorine inhibited concentration-dependently the outflow of 5-HT and 5-HIAA. Pirenzepine (0.03–0.1 μmol/l) which can discriminate between M1 and M2-receptor subtypes antagonized completely this inhibitory effect. In the presence of 1 μmol/l tetrodotoxin (TTx), all three muscarine receptor agonists increased the outflow of 5-HT and 5-HIAA. Oxotremorine 1 μmol/l was most effective and increased the outflow of 5-HT by 145%, that of 5-HIAA by 235%. McN-A-343 and pilocarpine, both at a concentration of 10 μmol/l, increased the outflow of 5-HT by about 40%, that of 5-HIAA by 50% and 71%, respectively. The stimulatory effect of oxotremorine was competitively antagonized by pirenzepine; a pA2 value of 7.70 was calculated. In conclusion, the cholinergic modulation of the release of 5-HT from the enterochromaffin cells consists of an indirect inhibitory (via the release of a neurotransmitter) and a direct stimulatory component. Muscarine receptors mediating the indirect effect may belong to the M1-subtype whereas the direct stimulatory effect may be mediated by a mixed population of M1 and M2 receptors or by a subtype of M1 receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00173575
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  • 6
    Electronic Resource
    Electronic Resource
    Modulation by 5-HT3 and 5-HT4 receptors of the release of 5-hydroxytryptamine from the guinea-pig small intestine (1993)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 347 (1993), S. 137-140 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00169258
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of vasoactive intestinal polypeptide on the release of serotonin from the in vitro vascularly perfused small intestine of guinea pig (1989)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 540-545 
    Details
    ISSN: 1432-1912
    Keywords: 5-HT release ; Enterochromaffin cells ; Vasoactive intestinal polypeptide (VIP) ; Peristaltic reflex
    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 endogenous serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) into the portal vein was measured. All test substances were intraarterially perfused. Vasoactive intestinal polypeptide (VIP, 1 pmol/l — 100 nmol/1) inhibited the spontaneous release of 5-HT and 5-HIAA. The maximal inhibitory effect (about 60%) was seen at 100 pmol/1. The effect of VIP on the spontaneous release of 5-HT and 5-HIAA was not changed in the presence of 1 μol/l tetrodotoxin (TTX). Raising intraluminal pressure by 500 Pa for 5 min increased the release of 5-HT and 5-HIAA by about 25%. Raising the intraluminal pressure in the presence of VIP reduced the release of 5-HT and 5-HIAA by about 75%. In the presence of TTX (1 gmol/l), raising intraluminal pressure also caused a decrease of the release of 5-HT and 5-HIAA which was unaffected by the additional presence of VIP. The fluid volume expelled during peristaltic activity was not affected by VIP, but reduced by about 90% in the presence of TTX. In conclusion the results demonstrate a direct inhibitory effect of VIP on the release of 5-HT from the enterochromaffin cells. In addition, VIP appears to interfere with the neuronally mediated stimulation of 5-HT release during peristaltic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00167258
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  • 8
    Electronic Resource
    Electronic Resource
    Effects of the benzodiazepine receptor agonist midazolam and antagonist flumazenil on 5-hydroxytryptamine release from guinea-pig intestine in vitro (1990)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 341 (1990), S. 1-7 
    Details
    ISSN: 1432-1912
    Keywords: Enterochromaffin cells ; 5-Hydroxytryptamine ; Guinea-pig intestine ; GABA ; Benzodiazepine receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated segments of the guinea-pig small intestine and the guinea-pig stomach were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxy-indoleacetic acid into the portal venous effluent determined by high pressure liquid chromatography with electrochemical detection. Test substances were applied intraarterially. The benzodiazepine receptor agonist, midazolam, concentration-dependently increased (by 58%, at 1 nmol/l) and decreased (by 32%, at 100 nmol/l) the release of 5-HT from small intestine preparations. Both effects were blocked by the benzodiazepine receptor antagonist flumazenil (10 nmol/l) The stimulatory effect of midazolam was also abolished in the presence of tetrodotoxin (1 μmol/l) or scopolamine (100 nmol/l). In the absence of tetrodotoxin, flumazenil (10 nmol/l) alone decreased the release of 5-HT from the small intestine by 41%, but it increased the release of 5-HT by 50% in the presence of tetrodotoxin. Both effects of flumazenil were abolished in the presence of bicuculline (50 μmol/l). In the absence of tetrodotoxin, flumazenil (10 nmol/l) decreased also the release of 5-HT and its metabolite from the perfused stomach by about 40%, whereas midazolam (1 nmol/l) caused an increase by about 60%. In conclusion, benzodiazepine receptors modulate the previously described intrinsic GABAergic regulation of 5-HT release from enterochromaffm cells in the guinea-pig intestine. It is suggested that an endogenous benzodiazepine-like substance of non-neuronal origin is present in the small intestine and stomach of the guinea-pig.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195050
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