Potential of GLP-1 receptors in emesis control in Suncus murinus (house musk shrew)

Abstract

Studies in rodents and ferrets have shown that GLP-1 containing neurons connect the brainstem emetic centres with forebrain areas involved in nausea and feeding. The aim of the present study was to use Suncus murinus, a species commonly used in emesis research, to investigate the mechanism of GLP-1-induced emesis and to examine if GLP-1 antagonists have anti-emetic properties. In conscious freely moving animals, the GLP-1 receptor agonist, exendin-4 (0.03–3 nmol, i.c.v.) induced emesis (P<0.01) and c-fos expression in the amygdala (P<0.01), hypothalamus (P<0.01) and brainstem (P<0.001), but failed to modify amino acid levels in these areas (P>0.05). The GLP-1 receptor antagonist, exendin (9–39) (30 nmol, i.c.v.), antagonized emesis induced by exendin-4, and the increases in c-fos expression (P<0.05). Conversely, ondansetron (3 μmol/kg, s.c.; P>0.05) failed to reduce emesis. In other studies, exendin (9–39), antagonized emesis and c-fos expression induced by the chemotherapeutic drug, cisplatin (30 mg/kg, i.p.; P<0.05), but not nicotine (5 mg/kg, s.c.; P>0.05), or copper sulphate pentahydrate (120 mg/kg, p.o.; P>0.05). These findings suggest that central GLP-1 may play a role in emesis control and that GLP-1 receptors may represent a potential target for anti-emetic development.