Separation of emetic and anorexic responses of exendin-4, a GLP-1 receptor agonist in Suncus murinus (house musk shrew)

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• 作者：Sze Wa Chan^a ; ^{stellacsw@cuhk.edu.hk} ; Ge Lin^b ; ^{linge@cuhk.edu.hk} ; David Tai Wai Yew^a ; ^{david-yew@cuhk.edu.hk} ; Chi Kong Yeung^a ; ^{yeungck@rocketmail.com} ; John A. Rudd^a ; ^{jar@cuhk.edu.hk}
• 关键词：Central nervous system ; Emesis ; Exendin-4 ; Exendin (9&ndash ; 39) ; GLP-1 receptors ; Suncus murinus
• 刊名：Neuropharmacology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：70
• 期：Complete
• 页码：141-147
• 全文大小：745 K

文摘

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. Therefore, the present studies investigated the potential of GLP-1 receptor ligands to modulate emesis and feeding in Suncus murinus. Exendin-4, a selective GLP-1 receptor agonist, was administered subcutaneously (1-30?nmol/kg) or intracerebroventricularly (0.03-3?nmol) after 12-h of fasting. In other studies, animals were pretreated with the GLP-1 receptor antagonist, exendin (9-39), or saline (5?¦Ìl) 15?min prior to exendin-4 (3?nmol, i.c.v.). Behaviour of animals and food and water intake were then recorded for 1-2?h; c-Fos expression was also assessed in the brains of animals in the i.c.v. studies. The subcutaneous administration of exendin-4 reduced food and water intake (p?<?0.001) and induced emesis in 40 % of animals (p?>?0.05). The intracerebroventricular administration of exendin-4 also prevented feeding, and induced emesis (p?<?0.01). In these studies, exendin (9-39) (30?nmol, i.c.v.) antagonised emesis induced by exendin-4 and the increased c-Fos expressions in the brainstem and hypothalamus (p?<?0.05), but it was ineffective in reversing the exendin-4-induced inhibition of food and water intake (p?>?0.05). These data suggest that exendin-4 exerts its emetic effects in the brainstem and/or hypothalamus via GLP-1 receptors. The action of exendin-4 to suppress feeding may involve non-classical GLP-1 receptors or other mechanisms.