Central glucagon like peptide-1 delays solid gastric emptying via central CRF and peripheral sympathetic pathway in rats

Abstract

It has been shown that glucagon like peptide-1 (GLP-1) acts on the central nervous system (CNS), in addition to its peripheral actions. Central administration of glucagon like peptide-1 (GLP-1) delays liquid gastric emptying via non-adrenergic, non-cholinergic neurons in rats. However, it remains unclear how central GLP-1 delays solid gastric emptying in rats. GLP-1 receptors at the CNS mediates the endocrine and anxiety responses to psychogenic and interoceptive stress. Corticotropin-releasing factor (CRF) is also known as a stress-related peptide, which delays gastric emptying of liquid and solid food via the autonomic nervous system. We have recently showed that central CRF delays solid gastric emptying via sympathetic pathways in rats. However, it remains unknown how central GLP-1 and CRF interact in mediating the inhibitory effect on solid gastric emptying. After a 24 h-fasting, GLP-1 was administered by intracisternal (ic)-injection immediately after the solid meal ingestion. Ninety minutes after the peptide injection, gastric contents were measured. Ic-injection of GLP-1 (30–3000 pmol) dose-dependently inhibited solid gastric emptying. Ic-injection of GLP-1 (3000 pmol)-induced delay of gastric emptying was partially antagonized by celiac ganglionectomy but not by atropine or N G-nitro- l-arginine methyl ester ( l-NAME). Ic-injection of a CRF antagonist, astressin (2.8 nmol), partially antagonized GLP-1-induced delay of solid gastric emptying. These results indicate that central CRF and peripheral sympathetic pathway are, at least in part, involved in mediating central GLP-1-induced delay of solid gastric emptying in rats.