GLP-1 receptor signaling contributes to anorexigenic effect of centrally administered oxytocin in rats.
The present study examined possible interactions between central glucagon-like peptide-1 (GLP-1) and oxytocin (OT) neural systems by determining whether blockade of GLP-1 receptors attenuates OT-induced anorexia and vice versa. Male rats were acclimated to daily 4-h food access. In the first experiment, rats were infused centrally with GLP-1 receptor antagonist or vehicle, followed by an anorexigenic dose of synthetic OT. Access to food began 20 min later. Cumulative food intake was measured every 30 min for 4 h. In the second experiment, rats were infused with OT receptor blocker or vehicle, followed by synthetic GLP-1 [(7-36) amide]. Subsequent food intake was monitored as before. The anorexigenic effect of OT was eliminated in rats pretreated with the GLP-1 receptor antagonist. Conversely, GLP-1-induced anorexia was not affected by blockade of OT receptors. In a separate immunocytochemical study, OT-positive terminals were found closely apposed to GLP-1-positive perikarya, and central infusion of OT activated c-Fos expression in GLP-1 neurons. These findings implicate endogenous GLP-1 receptor signaling as an important downstream mediator of anorexia in rats after activation of central OT neural pathways.
Rinaman
Linda
L
Department of Neuroscience, University of Pittsburgh, 446 Crawford Hall, Pittsburgh, PA 15260, USA. Rinaman@pitt.edu
Rothe
Elizabeth E
EE
D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D004435:Eating / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010121:Oxytocin / Q000008:administration & dosage* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000502:physiology*; D018045:Receptors, Oxytocin / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D018027:Receptors, Glucagon; D018045:Receptors, Oxytocin; C055453:glucagon-like peptide 1 (7-36)amide; D010121:Oxytocin; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon