The action of 5‐hydroxytryptamine, 5‐hydroxytryptophan and reserpine on intestinal peristalsis in anaesthetized guinea‐pigs

Bülbring, Edith; Crema, A.

doi:10.1113/jphysiol.1959.sp006176

Cited by 105 publications

(46 citation statements)

References 28 publications

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“…It is well established that 5-HT regulates motility by activating nerve terminals of intrinsic sensory neurons (4,8,9,15,17,23) and that a similar effect is seen with low (nanomolar) concentrations of fluoxetine (28). The present results indicate that fluoxetine-induced motor activity in isolated guinea pig duodenum and jejunum consists virtually exclusively of segmenting contractions that are largely blocked by luminal infusion of 5-HT 3 or 5-HT 4 receptor antagonists.…”

Section: Discussionsupporting

confidence: 50%

Serotonin and cholecystokinin mediate nutrient-induced segmentation in guinea pig small intestine

Ellis

Chambers

Gwynne

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ellis M, Chambers JD, Gwynne RM, Bornstein JC. Serotonin and cholecystokinin mediate nutrient-induced segmentation in guinea pig small intestine. Am J Physiol Gastrointest Liver Physiol 304: G749 -G761, 2013. First published February 7, 2013 doi:10.1152/ajpgi.00358.2012.-Segmentation is an important process in nutrient mixing and absorption; however, the mechanisms underlying this motility pattern are poorly understood. Segmentation can be induced by luminal perfusion of fatty acid in guinea pig small intestine in vitro and mimicked by the serotonin (5-HT) reuptake inhibitor fluoxetine (300 nM) and by cholecystokinin (CCK). Serotonergic and CCK-related mechanisms underlying nutrient-induced segmentation were investigated using selective 5-HT and CCK receptor antagonists on isolated segments of small intestine luminally perfused with 1 mM decanoic acid. Motility patterns were analyzed using video imaging and spatiotemporal maps. Segmenting activity mediated by decanoic acid was depressed following luminal application of the 5-HT receptor antagonists granisetron (5-HT3, 1 M) and SB-207266 (5-HT 4, 10 nM) and the CCK receptor antagonists devazepide (CCK-1, 300 nM) and L-365260 (CCK-2, 300 nM), but these antagonists did not further depress segmentation when combined. The P2 receptor antagonist pyridoxal phosphate-6-azophenyl-2=,4=-disulfonate (10 M) had no effect on activity. Serosal application of 5-HT antagonists had little effect on segmentation in the duodenum but reduced activity in the jejunum when granisetron and SB-207266 were applied together. These results reveal that 5-HT3 and 5-HT4 receptors, as well as CCK-1 and CCK-2 receptors, are critical in regulating decanoic acid-induced segmentation. Computational simulation indicated that these data are consistent with decanoic acid activating two pathways in the mucosa that converge within the enteric neural circuitry, while contraction-induced release of 5-HT from the mucosa provides feedback into the neural circuit to set the time course of the overall contractile activity. intestinal motility; decanoic acid; segmentation; serotonin; 5-HT3 receptors; 5-HT4 receptors; CCK-1 receptors; CCK-2 receptors DIGESTION AND MIXING of intestinal contents are accomplished through a complex, yet poorly understood, pattern of motility, called segmentation (11). Segmentation is a major feature of the small intestine in the "fed state" after a meal and comprises rhythmic local constrictions in the intestinal smooth muscle that are stationary or propagate only a short distance and occur as isolated bursts of motor activity. Despite its importance, the mechanisms controlling segmentation are yet to be determined.Fed-state motor activity consists of a mixture of propulsive and segmenting contractions, with the predominant type of contraction being determined, in part, by the nutrient composition of the meal. For example, nonnutritive meals produce predominantly propulsive contractile activity (propagating contractions, which propel content along the intestine) in the duodenum a...

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Section: Discussionsupporting

confidence: 50%

Serotonin and cholecystokinin mediate nutrient-induced segmentation in guinea pig small intestine

Ellis

Chambers

Gwynne

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…[1][2][3][4][5] Ondansetron, a 5-HT 3 receptor antagonist inhibits the nausea and vomiting associated with chemotherapy. An important side effect in such patients is constipation.…”

Section: Methodsmentioning

confidence: 99%

Effects of a 5‐HT₃ antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging

Marciani

Wright

Foley

et al. 2010

Aliment Pharmacol Ther

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SUMMARYBackground 5-HT 3 antagonists have been shown to be effective in relieving the symptoms of irritable bowel syndrome with diarrhoea (IBS-D). Using a recently validated magnetic resonance imaging (MRI) method, we have demonstrated reduced fasting small bowel water content (SBWC) in IBS-D associated with accelerated small bowel transit. We hypothesized that slowing of transit with ondansetron would lead to an increase in SBWC by inhibiting fasting motility.

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“…It is likely, therefore, that the fast contractile response of the intestine to 5-HTP was induced through 5-HT formed locally from the exogenously administered 5-HTP. On the other hand, Bulbring and Crerna (15) reported that the administration of 5-HTP into the mesenteric artery of the guinea-pig increased the release of 5-HT into the lumen of the intestine. Taking into consideration the facts that the fast contraction caused by 5-HTP appeared after a latent period of 30-60 sec., and that the doses required were about 10 times larger than those of 5-HT producing a similar effect, it may be assumed that the contractile response of the intestine to 5-HTP was mediated through the 5-HT released from the stores.…”

Section: Discussionmentioning

confidence: 99%

Comparative Studies With 5-Hydroxytryptamine and Its Derivatives in Isolated, Blood-Perfused Small Intestine and Tleum Strip of the Rat

Sakai¹,

Akima²,

Shiraki³

1979

Japanese Journal of Pharmacology

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Abstract--The mode of actions of' 5-hydroxytryptamine (5-HT) and its derivatives, tryptophan (14)), 5-hydroxytryptophan (5-HTP) and 5-hydroxyindole acetic acid(5-HIAA) vas studied on the isolated, blood-perfused small intestine and isolated ileum strip of rats.In the isolated, blood-perfused intestinal preparations, 5-HT and 5-HTP injected into the superior mesenteric artery caused a monophasic fast contraction, while TP and 5-HIAA had no effects on the intestine. The contractile responses to 5-HT and 5-HTP were abolished by tetrodotoxin (TTX), hexamethoitium (C5) and morphine, but were resistant to blockade of either atropine, methvsergidc or phentolamine.On the other hand, in the ileum strip preparations, 5-HT contracted the ileum, but its derivatives had no effects on the ileum. TTX, C,;, morphine and atropine failed to prevent the contractile response to 5-HT, whereas methysergide effectively antagonized the response. The present results indicate that 5-HT acts by exciting intramural neuronal elements or by directly contracting the smooth muscle of the intestine.5-HTP seems to act in the same manner as 5-HT.5-Hydroxytryptamine (5-HT) has been shown to contract smooth muscle of the isolated intestine by a direct action on the muscle fibres or by an indirect effect through excita tion of the intrinsic network of nerves (1-5). These findings, however, were obtained in isolated intestinal preparations bathed in physiological salt solutions. In view of this, it was considered that recordings of response of the intestinal smooth muscle with an intact blood supply may reveal features of the intestinal musculature.In the present experiments, we perfused the isolated small intestine of the rat through the superior mesenteric artery with blood from a donor, using a cross-circulation technique. This method enabled injection of drugs into the superior mesenteric artery and We could observe simultaneously vascular and muscular responses of the intestine.Our objective herein was to determine whether comparable information about the actions of 5-HT and its derivatives could he obtained from isolated, blood-perfused small intestine and from isolated ileum strips of the rat. MA I"ERIALS AND M1 THODSMale Sprague-Dawley rats were used.Isolated, 1,/crcnl perJuse~l.enrall intestinc: Donor rats (550-750 g) were anesthetized with pentobarbital sodium (65 mg/kg i.p.). The animal was placed on a table maintained by a

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The action of 5‐hydroxytryptamine, 5‐hydroxytryptophan and reserpine on intestinal peristalsis in anaesthetized guinea‐pigs

Cited by 105 publications

References 28 publications

Serotonin and cholecystokinin mediate nutrient-induced segmentation in guinea pig small intestine

Serotonin and cholecystokinin mediate nutrient-induced segmentation in guinea pig small intestine

Effects of a 5‐HT₃ antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging

Comparative Studies With 5-Hydroxytryptamine and Its Derivatives in Isolated, Blood-Perfused Small Intestine and Tleum Strip of the Rat

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The action of 5‐hydroxytryptamine, 5‐hydroxytryptophan and reserpine on intestinal peristalsis in anaesthetized guinea‐pigs

Cited by 105 publications

References 28 publications

Serotonin and cholecystokinin mediate nutrient-induced segmentation in guinea pig small intestine

Serotonin and cholecystokinin mediate nutrient-induced segmentation in guinea pig small intestine

Effects of a 5‐HT3 antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging

Comparative Studies With 5-Hydroxytryptamine and Its Derivatives in Isolated, Blood-Perfused Small Intestine and Tleum Strip of the Rat

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Effects of a 5‐HT₃ antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging