Response heterogeneity of 5-HT3 receptor antagonists in a rat visceral hypersensitivity model

Langlois, A.; Pascaud, X.; Junien, J.L.; Dahl, Svein G.; Rivière, Pierre

doi:10.1016/s0014-2999(96)00857-6

Cited by 32 publications

(26 citation statements)

References 13 publications

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“…The peripherally acting 5-HT 3 receptor antagonist alosetron blunts responses to colorectal distension in experimental animals and improves discomfort and pain in a subgroup of patients with functional bowel disorders (Camilleri et al, 1999;Kozlowski et al, 2000). Interestingly, other 5-HT 3 receptor antagonists do not consistently affect visceral pain in experimental animals or humans (Langlois et al, 1996;Kim and Camilleri, 2000). Less is known about the effects of agonists and antagonists of metabotropic 5-HT receptors on visceral sensation.…”

Section: Discussionmentioning

confidence: 99%

TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation

Sugiuar

Bielefeldt²,

Gebhart³

2004

J. Neurosci.

125

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Using whole-cell patch-clamp methods, we examined the hypothesis that serotonin [5-hydroxytryptamine (5-HT)] receptor activation enhances TRPV1 function in mouse colon sensory neurons in lumbosacral dorsal root ganglia, which were identified by retrograde labeling with DiI (1,1Ј-dioctadecyl-3,3,3Ј,3-tetramethlindocarbocyanine methanesulfonate) injected into multiple sites in the wall of the descending colon. 5-HT increased membrane excitability at a temperature below body temperature in response to thermal ramp stimuli in colon sensory neurons from wild-type mice, but not from TRPV1 knock-out mice. 5-HT significantly enhanced capsaicin-, heat-, and proton-evoked currents with an EC 50 value of 2.2 M. 5-HT (1 M) significantly increased capsaicin-evoked (100 nM) and proton-evoked (pH 5.5) currents 1.6-and 4.7-fold, respectively, and significantly decreased the threshold temperature for heat current activation from 42 to 38°C.

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Section: Discussionmentioning

confidence: 99%

TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation

Sugiuar

Bielefeldt²,

Gebhart³

2004

J. Neurosci.

125

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“…The procedures for the maintenance and use of experimental animals were carried out in accordance with the guidelines of the International Association for the Study of Pain. CRDacetic acid-induced visceral hypersensitivity was triggered according to the method of Langlois et al (1996). 11) Briefly, each animal was fasted overnight, placed in a transparent plastic cage lined with sawdust, and allowed 60 min to acclimatize.…”

Section: Methodsmentioning

confidence: 99%

“…We generated an in vivo CRD-acetic acid-induced visceral hypersensitivity model in rats and examined the effect of GTS on this model. 11) We first tested reproducibility of our procedure in the absence of drug treatment. We observed a small number of abdominal contractions after intracolonic administration of saline followed by distension at 30 mmHg for 10 min (8.1Ϯ2.4 abdominal contractions during the distension period).…”

Section: )mentioning

confidence: 99%

“…We induced experimental visceral hypersensitivity by colorectal distention (CRD) and intracolonic infusion of 0.6% acetic acid (CRD-acetic acid) in rats, 11) and examined the effect of ginsenosides (GTS, PT or PD) on CRD-acetic acid-induced visceral hypersensitivity as compared to the effect of zacopride, a known 5-HT 3 receptor antagonist. We found that ginsenosides dose-dependently reduced CRD-acetic acid-induced visceral hypersensitivity, with the PT ginsenosides showing a more significant effect than the PD ginsenosides.…”

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confidence: 99%

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Effect of Ginseng Saponins on a Rat Visceral Hypersensitivity Model

Kim

Lee

Jeong

et al. 2005

Biological & Pharmaceutical Bulletin

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One of the most common gastrointestinal disorders without direct bacterial or viral infection is irritable bowel syndrome (IBS), which is strongly associated with stress. The most common IBS symptoms are abnormal visceral discomfort, pain and diarrhea. Although the precise mechanism of IBS has not been fully elucidated, some symptoms of IBS are thought to involve the 5-hydroxytryptamine receptor 3 (5-HT 3 ). Zacopride, a 5-HT 3 -receptor antagonist, has been used to effectively treat diarrhea-predominant IBS patients with abdominal pain and bowel discomfort. 1) However, other 5-HT 3 receptor antagonists have demonstrated a wide heterogeneity of potency and efficacy against visceral pain; granisetron reduces rectal sensitivity in IBS patients, but ondansetron does not.2,3) These and other findings seem to indicate that the 5-HT 3 receptors are associated with the nociceptive processes of visceral pain in both humans and animals, 4) but the precise mechanisms by which 5-HT 3 -receptor antagonists inhibit the visceral pain remain unclear. Researchers are currently seeking to identify new 5-HT 3 -receptor antagonists capable of blocking abnormal visceral perception without deleterious side effects.Ginseng, the root of Panax ginseng C. A. MEYER, is well known for restoring and promoting human health. In traditional medicine, ginseng has been used as an antidote for stress and to alleviate disorders such as anorexia, dyspepsia, pain and vomiting.5) The main molecular components responsible for the actions of Panax ginseng are the ginsenosides, which are also known as ginseng saponins. Approximately 30 different ginsenoside forms have been isolated and identified from the root of Panax ginseng. These molecules have a four-ring, steroid-like structure bearing sugar moieties, and can be classified into protopanaxadiol (PD) or protopanaxatriol (PT) ginsenosides according to the position of the sugar moieties at carbon-3 or -6 (Fig. 1).6) Ginsenosides regulate several types of ligand-gated ion channel activity, and differential regulation is seen by the PT and PD forms. In cells expressing nicotinic acetylcholine receptors, such as bovine chromaffin cells, the PT ginsenosides, especially ginsenosides Rf and Rg 2 , potently inhibit acetylcholine-stimulated Na ϩ influx. 7) Choi et al. (2002) and Sala et al. (2002) showed that PT ginsenosides potently inhibited acetylcholine-induced inward currents in Xenopus oocytes expressing several subtypes of neuronal and muscle-type nicotinic acetylcholine receptors. 8,9) Lee et al. (2004) showed that PT ginsenosides and the PT ginsenoside metabolite, M4, inhibited 5-HT-mediated inward currents in Xenopus oocytes expressing 5-HT 3A receptors to a greater degree than did PD ginsenosides and the PD ginsenoside metabolite, Compound K.10) Since 5-HT 3A receptors exist in enteric nervous systems and are involved in IBS, the observation that ginsenosides can block 5-HT 3A receptor channel activity suggests that ginsenosides might alleviate IBS. However, no previous work has examined whether t...

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“…Study 6: Acute colonic hypersensitivity was induced as described by Langlois et al (26) and Plourde et al (27). Briefly, male SD rats (300-400 g) were fasted overnight, anesthetized with 3% isoflurane and administered with an intracolonic infusion of dilute acetic acid (0.6%; 1.5 ml).…”

Section: Visceromotor Responses (Vmr) To Colorectal Distension (Crd)mentioning

confidence: 99%

Prokinetic effects of LD02GIFRO on functional gastrointestinal disorder in rats

Choi

Zheng

Park³

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. LD02GIFRO is a novel prokinetic agent formulated with Poncirus fructus and Zanthoxylum sp. fruits. The aim of the present study was to evaluate the effect of LD02GIFRO on delayed gastrointestinal transit (GIT) and colorectal hypersensitivity. To investigate the effect of LD02GIFRO, a rat model of delayed GIT was induced via three mechanisms; postoperative ileus (POI), morphine, and POI plus morphine. Visceromotor responses (VMR) to colorectal distension (CRD) were also evaluated. POI was induced by laparotomy surgery and manipulation of the small intestine under anesthesia, and GIT was calculated by measuring the length that Evans Blue travelled through the gastrointestinal tract in a given time. Oral administration of 260 mg/kg LD02GIFRO caused Evans Blue to migrate significantly further in the delayed GIT models induced by POI, morphine and POI plus morphine compared with the control (P<0.05). This effect was inhibited by atropine, a muscarinic receptor antagonist, and completely abolished by GR125487, a 5-HT 4 -receptor antagonist. Furthermore, intraperitoneal administration of 600 and 900 mg/kg LD02GIFRO significantly reduced VMR to CRD in acute and chronic colorectal hypersensitive rat models, induced by acetic acid and trinitrobenzenesulfonic acid, to almost normal levels (P<0.01). In the present study, LD02GIFRO successfully ameliorated delayed GIT models and colorectal hypersensitivity models, suggesting that LD02GIFRO may be an effective therapeutic treatment for patients with functional gastrointestinal disorders and abnormalities in GIT.

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Response heterogeneity of 5-HT3 receptor antagonists in a rat visceral hypersensitivity model

Cited by 32 publications

References 13 publications

TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation

TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation

Effect of Ginseng Saponins on a Rat Visceral Hypersensitivity Model

Prokinetic effects of LD02GIFRO on functional gastrointestinal disorder in rats

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