Sympathetic pathways mediate GLP-1 actions in the gastrointestinal tract of the rat

Abstract

The aim of this study was to establish the actions of GLP-1 (7-37) on gastrointestinal motility in rats. We prepared anaesthetized Sprague-Dawley rats with strain-gauges in the antrum, duodenum and the proximal jejunum and a catheter in the aorta close to the coeliac artery for close infusion of substances. Intraarterial GLP-1 infusions (3×10 −10 and 3×10 −9 moles/kg per 10 min) ( n=8) induced inhibition of spontaneous motor activity in the antrum, duodenum and proximal jejunum. Inhibition induced by GLP-1 was reversed by i.v. infusion of GLP-1 receptor antagonist, Exendin (9-39) (3×10 −8 moles/kg per 10 min) ( n=6). Neither the presence of l-NNA (10 −5 moles/kg) ( n=9) nor the VIP receptor antagonist [4-Cl-D-Phe 6, Leu 17 ]-VIP (3×10 −8 moles/kg per 10 min) ( n=8) modified responses to GLP-1. However, a combination of the adrenergic blockers phentolamine and propranolol (1 mg/kg each) ( n=8) completely blocked motor actions of GLP-1 in all the organs studied. Moreover, inhibition of gastrointestinal motor activity by GLP-1 was blocked by previous infusion of hexamethonium (10 mg/kg) ( n=4). This study demonstrates that GLP-1 inhibits gastrointestinal motor activity of the rat acting on specific GLP-1 receptors and via stimulation of adrenergic pathways.