title: The differential antiemetic properties of GLP-1 receptor antagonist, exendin (9-39) in Suncus murinus (house musk shrew).
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.
authors.affiliation: Emesis Research Group, Neuro-degeneration, Development and Repair, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Electronic address: swchan@cihe.edu.hk.
authors.forename: Sze Wa
authors.initials: SW
authors.lastname: Chan
authors.affiliation: Emesis Research Group, Neuro-degeneration, Development and Repair, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Electronic address: jack_fun007@hotmail.com.
authors.forename: Zengbing
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Cancer and Inflammation, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Electronic address: linge@cuhk.edu.hk.
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
authors.affiliation: Emesis Research Group, Neuro-degeneration, Development and Repair, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Electronic address: david-yew@cuhk.edu.hk.
authors.forename: David Tai Wai
authors.initials: DT
authors.lastname: Yew
authors.affiliation: Emesis Research Group, Neuro-degeneration, Development and Repair, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Electronic address: yeungck@rocketmail.com.
authors.forename: Chi Kong
authors.initials: CK
authors.lastname: Yeung
authors.affiliation: Emesis Research Group, Neuro-degeneration, Development and Repair, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Electronic address: jar@cuhk.edu.hk.
authors.forename: John A
authors.initials: JA
authors.lastname: Rudd
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D010880:Piperidines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D012788:Shrews; D014688:Venoms; D014839:Vomiting / Q000139:chemically induced / Q000378:metabolism
chemical_list: D000932:Antiemetics; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D010455:Peptides; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D018027:Receptors, Glucagon; D014688:Venoms; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D017294:Ondansetron; C083773:exendin (9-39); D000077270:Exenatide
keywords: Central nervous system; Cisplatin; Emesis; Exendin (9–39); GLP-1 receptors; Suncus murinus