Abstract |
The use of glucagon-like peptide-1 (7-36) amide (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus is commonly associated with nausea and vomiting. Previous studies using Suncus murinus revealed that the GLP-1 receptor agonist, exendin-4, induces emesis via the brainstem and/or hypothalamus. The present study investigated the mechanism of exendin-4-induced emesis in more detail. Ondansetron (1 mg/kg, s.c.) and CP-99,994 (10 mg/kg, s.c) failed to reduce emesis induced by exendin-4 (3 nmol, i.c.v.), suggesting that 5-HT3 and NK1 receptors are not involved in the mechanism. In other studies, the GLP-1 receptor antagonist, exendin (9-39), antagonised emesis and c-Fos expression in the brainstem and the paraventricular hypothalamus induced by the chemotherapeutic drug cisplatin (30 mg/kg, i.p.; p < 0.05), but not the emesis induced by nicotine (5 mg/kg, s.c.; p > 0.05), or copper sulphate pentahydrate (120 mg/kg, p.o.; p > 0.05). GLP-1 receptors may therefore represent a potential target for drugs to prevent chemotherapy-induced emesis in situations where 5-HT3 and NK1 receptor antagonists fail.
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Authors | Sze Wa Chan, Zengbing Lu, Ge Lin, David Tai Wai Yew, Chi Kong Yeung, John A Rudd |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 83
Pg. 71-8
(Aug 2014)
ISSN: 1873-7064 [Electronic] England |
PMID | 24726308
(Publication Type: Journal Article)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antiemetics
- Glucagon-Like Peptide-1 Receptor
- Peptide Fragments
- Peptides
- Piperidines
- Proto-Oncogene Proteins c-fos
- Receptors, Glucagon
- Venoms
- 3-(2-methoxybenzylamino)-2-phenylpiperidine
- Ondansetron
- exendin (9-39)
- Exenatide
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Topics |
- Animals
- Antiemetics
(pharmacology)
- Brain
(metabolism)
- Exenatide
- Glucagon-Like Peptide-1 Receptor
- Male
- Ondansetron
(pharmacology)
- Peptide Fragments
(pharmacology)
- Peptides
- Piperidines
(pharmacology)
- Proto-Oncogene Proteins c-fos
(metabolism)
- Receptors, Glucagon
(antagonists & inhibitors)
- Shrews
- Venoms
- Vomiting
(chemically induced, metabolism)
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