SYMPATHETIC PATHWAYS MEDIATE GLP-1 ACTIONS IN THE GASTROINTESTINAL-TRACT OF THE RAT

The aim of this study was to establish the actions of GLP-1 (7-37) on gastrointestinal motility in rats. We prepared anaesthetized Sprague-D awley rats with strain-gauges in the antrum, duodenum and the proximal jejunum and a catheter in the aorta close to the coeliac artery for c lose infusion of substances. Intraarterial GLP-1 infusions (3 x 10(-10 ) and 3 x 10(-9) moles/kg per 10 min) (n = 8) induced inhibition of sp ontaneous motor activity in the antrum, duodenum and proximal jejunum. Inhibition induced by GLP-1 was reversed by i.v. infusion of GLP-1 re ceptor antagonist, Exendin (9-39) (3 x 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)]-VTP (3 x 10(-8) moles /kg per 10 min) (n = 8) modified responses to GLP-1. However, a combin ation of the adrenergic blockers phentolamine and propranolol (1 mg/kg each) (n = 8) completely blocked motor actions of GLP-1 in all the or gans 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 s timulation of adrenergic pathways. (C) 1998 Elsevier Science B.V.