Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In general, rats and mice have not been used in research on emesis because they do not vomit. However, emetogenic stimuli such as anticancer drugs, apomorphine, copper sulfate and rotation induced pica, a behavior characterized by eating nonfood substances such as kaolin, in rats. We also found that cisplatin induced pica in mice, but it was rather difficult to determine the exact kaolin consumption in this species. In this study, we prepared kaolin pellets mixed with carmine, a dye not absorbed in the gastrointestinal tract, and estimated kaolin consumption by determination of carmine excreted in feces. Cisplatin (5 mg/kg) caused a significant increase in kaolin consumption (saline: 0.15 +/- 0.08 g vs. cisplatin: 0.45 +/- 0.16 g) and pretreatment with the 5-HT3 receptor antagonist, ondansetron (2 mg/kg), suppressed the increased consumption (vehicle: 0.33 +/- 0.05 g vs. ondansetron: 0.13 +/- 0.04 g). These findings suggested that the exact kaolin consumption could be quantified by the determination of carmine in feces and that mice could be useful for studying emesis.
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PMID:Pica in mice as a new model for the study of emesis. 1208 74

We investigated whether radiation-induced pica, a behavior characterized by the eating of a non-food substance, such as kaolin, can be used as an index of radiation-induced vomiting in rats. Since there was an individual difference in the susceptibility to pica, we selected rats that actually ate kaolin following X-ray irradiation, and used them for the experiment. The total-body irradiation (TBI) increased kaolin consumption in a dose-dependent manner (sham, 0.05 +/- 0.03 (SEM) g; 2 Gy, 0.38 +/- 0.11 g; 4 Gy, 1.54 +/- 0.28 g; 8 Gy, 3.55 +/- 0.67 g), and the increased kaolin consumption after 4 Gy of TBI was inhibited by a pretreatment with the serotonin 5-HT3 receptor antagonist ondansetron (2 mg/kg, i.p.) (saline, 1.49 +/- 0.33 g; ondansetron, 0.75 +/- 0.11 g). Furthermore, 4 Gy of abdominal irradiation was more effective to induce pica than that of head irradiation (abdomen: 0.37 +/- 0.05 g, head: 0.06 +/- 0.01 g). These findings suggested that peripheral serotonergic pathway is predominantly involved in the development of radiation-induced pica in rats and that the radiation-induced pica could be useful as a behavioral index for the severity of radiation-induced vomiting in rats.
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PMID:Establishment of an animal model for radiation-induced vomiting in rats using pica. 1223 27

Radiation sickness is frequently observed in total body irradiation (TBI). We have reported that the kaolin ingestion behavior "pica" may be analogous to nausea and vomiting in mice. We evaluated the effects of anti-emetics on the prevention of radiation-induced pica in mice. After the intraperitoneal injection of ondansetron (OND: 2 mg/kg), dexamethasone (DEX: 2 mg/kg) or CP-99,994 (CP: 15 mg/kg), mice received 9 Gy of TBI, and then kaolin consumption was measured after 24 h. Radiation-induced pica was slightly inhibited by pretreatment with a single administration of OND or DEX, but not by CP (control: 0.69+/-0.19 g, OND: 0.33+/-0.06 g, DEX: 0.39+/-0.07 g, CP: 0.66+/-0.09 g); it was significantly inhibited by the combination treatment of OND and DEX (control: 0.55+/-0.09 g, OND+DEX: 0.30+/-0.06 g, OND+CP: 0.70+/-0.04 g, DEX+CP: 0.58+/-0.02 g). The combination of the three drugs completely abolished the behavior (control: 0.67+/-0.08 g, OND+DEX+CP: 0.10+/-0.05 g). These results suggest that radiation-induced pica in mice may be useful to evaluate drugs for treatment of radiation sickness and that the combination therapy of a serotonin 5-HT3 receptor antagonist and a glucocorticosteroid with a neurokinin NK1 receptor antagonist is effective in reducing the symptom.
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PMID:Ondansetron, dexamethasone and an NK1 antagonist block radiation sickness in mice. 1609 69

This study aimed to dissect the mechanisms involved in malaise induced by the anti-cancer drug cisplatin by attempting to uncouple its effects on locomotor activity, arguably at least partly indicative of fatigue, from those effects indicative of emesis (pica, gastric stasis, reduced food intake) using pharmacological agents in the rat. Over 2 days cisplatin (6 mg/kg i.p.) reduced food intake, stimulated kaolin consumption, increased the wet weight of gastric contents and reduced locomotor activity. In animals treated with cisplatin: the 5-HT3 receptor antagonist ondansetron (1 mg/kg s.c. bd.) had no effect on either activity or weight of gastric contents but did increase food intake on day 1 (P<0.05) and the total over both days (27.6+/-1.8 vs. 19.9+/-2.3g, P<0.05), reducing kaolin consumption on day 2 (P<0.01) but not the total over both days; the NK1 receptor antagonist GR205171 (1 mg/kg s.c. bd.) was without effect on activity, but reduced the wet weight of gastric contents (P<0.05), increased food intake on day 2 (P<0.01) and total consumption over both days (28.1+/-1.7 g vs. 19.9+/-2.3 g; P<0.05) and reduced kaolin consumption on day 2 (P<0.05) but not over both days; dexamethasone (2 mg/kg s.c. bd.) blocked the cisplatin-induced reduction in activity on days 1 and 2 (P<0.01), reduced the wet weight of gastric contents by 43% (P<0.01), reduced kaolin consumption on both days (P<0.01) and arguably decreased the reduction in food intake caused by cisplatin. This study has revealed novel insights into the different spectra of activities of 5-HT3 and NK1 receptor antagonists and dexamethasone, which have implications for therapeutic strategies to alleviate the emetic, anorectic, dyspeptic and activity-reducing effects of anti-cancer chemotherapy.
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PMID:Differential effects of dexamethasone, ondansetron and a tachykinin NK1 receptor antagonist (GR205171) on cisplatin-induced changes in behaviour, food intake, pica and gastric function in rats. 1714 Dec 13