Potential role 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.