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-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 x 10(-10) and 3 x 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 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-Phe6, Leu17]-VIP (3 x 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.
Giralt
M
M
Department of Cell Biology and Physiology, Veterinary School, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Vergara
P
P
D000818:Animals; D004064:Digestive System / Q000294:innervation*; D005769:Gastrointestinal Motility / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D008297:Male; D016065:Myoelectric Complex, Migrating / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D011498:Protein Precursors / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology*
D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon