Separation of emetic and anorexic responses of exendin-4, a GLP-1 receptor agonist in Suncus murinus (house musk shrew)
Author(s)
Author(s)
Lin, G.
Yew, D. T. W.
Yeung, C. K.
Rudd, J. A.
Date Issued
2013
Publisher
Elsevier
Journal
Neuropharmacology
Volume
70
Start page
141
End page
147
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. 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 μl) 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.
SFU Affiliated Publication
No
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