Looking beyond 5-HT3 receptors: A review of the wider role of serotonin in the pharmacology of nausea and vomiting

Johnston, Kevin; Lu, Zhonghua; Rudd, John A.

doi:10.1016/j.ejphar.2013.10.014

Cited by 52 publications

(36 citation statements)

References 155 publications

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“…The relative effects of different agents that interfere with the synthesis, storage or release of 5‐HT are governed by their ability to reach different anatomical areas, populated by specific receptors. There is previous evidence for an involvement of 5‐HT1‐4R in emesis control, which is similar with earlier DON research (Johnston et al , ; Prelusky & Trenholm, ). However, there is still a question how 5‐HT and its subunit(s) control the emesis activity or are involved in it.…”

Section: Some Prospective Sights For Future Scientific Researches Andsupporting

confidence: 88%

Current and prospective sights in mechanism of deoxynivalenol‐induced emesis for future scientific study and clinical treatment

Chen

Zhao

Nüssler

et al. 2017

J of Applied Toxicology

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Deoxynivalenol (DON), one of trichothecene mycotoxins produced by the fungus Fusarium, is commonly detected in cereal foods and in secondary food production across the world. Lower concentrations of DON induce a dose-related feed refusal (anorexia), whereas it acts as a potent emetic agent at higher levels. DON-induced emesis in humans and livestock can be observed and recorded in both undeveloped and developed regions such as Lixian, Guide and Huangzhong in China and Illinois in the USA. Some studies with different animal models (pigs and minks) suggested that DON could change expressions of 5-hydroxytryptamine, peptide YY, neuropeptide Y2 receptor and nucleobindin-2/nesfatin-1 in plasma and different areas of the brain. Some selective antagonist of 5-hydroxytryptamine 3 receptors can inhibit DON-induced emetic response. Otherwise, the Ca homeostasis and MAPK pathway could be potential directions in future studies. Dolasetron, dantrolene and JNJ-31020028 can be used in clinical treatment but they have potential toxic effects. (-)Epicatechin, ginger phytochemicals and isoflavone can be tested in in vitro and in vivo for their usage as food additives for reducing the emesis. The present review summarizes and discusses some information from previous and recent prominent publications with the aim to provide some comprehensive and helpful data for understanding the mechanism of DON-induced emesis. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Some Prospective Sights For Future Scientific Researches Andsupporting

confidence: 88%

Current and prospective sights in mechanism of deoxynivalenol‐induced emesis for future scientific study and clinical treatment

Chen

Zhao

Nüssler

et al. 2017

J of Applied Toxicology

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“…Activation of 5-HT 3 Rs by 5-HT can evoke vomiting (Darmani and Ray, 2009; Johnston et al, 2014). In this study, 5-HT-immunoreactive fibers are most concentrated in the area within the NTS defined as the dorsomedial region (Phifer and Berthoud, 1998; Pool et al, 2007; Zheng et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Intracellular emetic signaling evoked by the L-type Ca2+ channel agonist FPL64176 in the least shrew (Cryptotis parva)

Zhong

Chebolu

Darmani

2018

European Journal of Pharmacology

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Ca2+ plays a major role in maintaining cellular homeostasis and regulates processes including apoptotic cell death and side-effects of cancer chemotherapy including vomiting. Currently we explored the emetic mechanisms of FPL64176, an L-type Ca2+ channel (LTCC) agonist with maximal emetogenic effect at its 10 mg/kg dose. FPL64176 evoked c-Fos immunoreactivity in shrew brainstem sections containing the vomit-associated nuclei, nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus. FPL64176 also increased phosphorylation of proteins ERK1/2, PKCα/βII and Akt in the brainstem. Moreover, their corresponding inhibitors (PD98059, GF 109203X and LY294002, respectively) reduced FPL64176-evoked vomiting. A 30 min subcutaneous (s.c.) pretreatment with the LTCC antagonist nifedipine (10 mg/kg) abolished FPL64176-elicited vomiting, c-Fos expression, and emetic effector phosphorylation. Ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs) mediate intracellular Ca2+ release from the sarcoplasmic/endoplasmic reticulum. The RyR antagonist dantrolene (i.p.), or a combination of low doses of nifedipine and dantrolene, but not the IP3R antagonist 2-APB, significantly attenuated FPL64176-induced vomiting. The serotonin type 3 receptor (5-HT3R) antagonist palonosetron (s.c.), the neurokinin 1 receptor (NK1R) antagonist netupitant (i.p.) or a combination of non-effective doses of netupitant and palonosetron showed antiemetic potential against FPL64176-evoked vomiting. Serotonin (5-HT) and substance P immunostaining revealed FPL64176-induced emesis was accompanied by an increase in 5-HT but not SP-immunoreactivity in the dorsomedial subdivision of the NTS. These findings demonstrate that Ca2+ mobilization through LTCCs and RyRs, and subsequent emetic effector phosphorylation and 5-HT release play important roles in FPL64176-induced emesis which can be prevented by 5-HT3R and NK1R antagonists.

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“…Granisetron blocked cisplatin‐induced bedding intake and gastric dysmotility, mainly during the first 2 hours after administration. Immediately after administration, cisplatin induces the massive release of serotonin from the enterochromaffin cells and this effect directly accounts for gastric dysmotility . The serotonin receptors involved in this immediate effect of cisplatin, located on vagal afferents innervating the upper gastrointestinal tract, are mainly of the 5‐HT 3 type, and thus granisetron and other antiemetics sharing the same mechanism of action are useful to prevent this effect, facilitate gastric emptying and block gastric (forestomach) distension …”

Section: Discussionmentioning

confidence: 99%

Alterations of colonic sensitivity and gastric dysmotility after acute cisplatin and granisetron

Martín‐Ruíz

Uranga

Mosińska

et al. 2018

Neurogastroenterology Motil

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Background Cisplatin is a highly emetogenic antineoplastic drug and induces peripheral neuropathy when given in cycles. Granisetron, a 5‐HT3 antagonist, is clinically used to prevent chemotherapy‐induced nausea/emesis and abdominal pain in irritable bowel syndrome. The effects of cisplatin on visceral sensitivity and those of granisetron in the context of cancer chemotherapy are not well known. Methods Adult male Wistar rats received two intraperitoneal injections 30 minutes apart: granisetron (1 mg kg−1)/vehicle and cisplatin (6 mg kg−1)/vehicle. Thereafter, nausea‐like behavior was measured as bedding intake for 4 hours, and gastric dysmotility was measured radiographically for 8 hours. Gastric weight and size were determined ex vivo and samples of the forestomach, corpus, ileum, and colon were obtained for histological analysis at 4 and 30 hours after cisplatin/vehicle. Visceral sensitivity was measured as abdominal contractions in response to mechanical intracolonic stimulation 2 hours after cisplatin/vehicle. Key Results Cisplatin‐induced bedding intake and gastric dysmotility, and granisetron blocked these effects, which occurred in the absence of frank mucositis. Visceral sensitivity was reduced to a similar extent by both drugs alone or in combination. Conclusions and Inferences Cisplatin‐induced bedding intake and gastric dysmotility were blocked by granisetron, confirming the involvement of serotonin acting on 5‐HT3 receptors. Unexpectedly, visceral sensitivity to colonic distension was reduced, to the same extent, by cisplatin, granisetron, and their combination, suggesting important mechanistic differences with nausea and gastric dysmotility that warrant further investigation.

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Looking beyond 5-HT3 receptors: A review of the wider role of serotonin in the pharmacology of nausea and vomiting

Cited by 52 publications

References 155 publications

Current and prospective sights in mechanism of deoxynivalenol‐induced emesis for future scientific study and clinical treatment

Current and prospective sights in mechanism of deoxynivalenol‐induced emesis for future scientific study and clinical treatment

Intracellular emetic signaling evoked by the L-type Ca2+ channel agonist FPL64176 in the least shrew (Cryptotis parva)

Alterations of colonic sensitivity and gastric dysmotility after acute cisplatin and granisetron

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