GLP-1-induced anorectic and emetic responses are mediated via exendin (9-39)-sensitive mechanisms in Suncus murinus

Abstract

Introduction. GLP-1 receptor agonists can be associated with nausea, emesis and reduced appetite in man. Our previous studies showed that the GLP-1 receptor agonists, GLP-1 (7-36) amide and exendin-4, inhibited feeding and water intake, and induced emesis in Suncus murinus.

Aims. In the present study, we examine if the action of GLP-1 (7-36) to induce emesis and inhibit feeding are mediated via central GLP-1 receptors using the potent GLP-1 receptor antagonist, exendin (9-39).

Methods. Suncus murinus were anaesthetised with sodium pentobarbitone (40 mg/kg, i.p.) and then stereotaxically implanted with a guide cannula into the lateral ventricle and allowed a 7-days recovery before experimentation. Animals were fasted 12-h prior to administration of drugs. On the day experimentation, they were administered exendin (9-39) (30 nmol, i.c.v.), or saline (5 μl i.c.v.) 15 min prior to GLP-1 (7-36) (3 nmol, i.c.v.), or saline (5 μl, i.c.v.). Food and water consumption and behaviour were measured for 1-h.

Results. GLP-1 (7-36) inhibited food and water intake (P<0.001) and induced emesis in 1 out of 6 animals. GLP-1 (7-36) also reduced significantly the distance moved when compared with the control group (P<0.05) and increased the duration of lying flat behaviour (P<0.001). Exendin (9-39) antagonized the effect of GLP-1 (7-36) on feeding and drinking, and lying flat behaviour (P<0.01). None of the animals pretreated with exendin (9-39) exhibited emesis.

Discussion. The data suggests that the action of GLP-1 (7-36) in the brain is probably mediated via GLP-1 receptors. The studies were fully supported by a grant from the Research Grants Council of the Hong Kong SAR, China (Project no. UGC/FDS11/M02/15).