Anorectic actions of prolactin-releasing peptide are mediated by corticotropin-releasing hormone receptors.
Prolactin-releasing peptide (PrRP) reduces food intake and body weight and modifies body temperature when administered centrally in rats, suggesting a role in energy homeostasis. However, the mediators of PrRP's actions are unknown. The present study, therefore, first examined the possible involvement of the anorectic neuropeptides corticotropin-releasing hormone (CRH) and the melanocortins (e.g., alpha-melanocyte-stimulating hormone) in PrRP's effects on food intake and core body temperature and, second, determined if PrRP affects energy expenditure by measuring oxygen consumption (Vo2). Intracerebroventricular injection of PrRP (4 nmol) to 24-h-fasted male Sprague-Dawley rats decreased food intake and modified body temperature. Blockade of central CRH receptors by intracerebroventricular coadministration of the CRH receptor antagonist astressin (20 microg) reversed the PrRP-induced reduction in feeding. However, astressin's effect on PrRP-induced changes in body temperature was complicated because the antagonist itself caused a slight rise in body temperature. In contrast, intracerebroventricular coadministration of the melanocortin receptor-3/4 antagonist SHU-9119 (0.1 nmol) had no effect on any of PrRP's actions. Finally, intracerebroventricular injection of PrRP (4 nmol) caused a significantly greater Vo2 over a 3-h test period compared with vehicle-treated rats. These results show that the anorectic actions of PrRP are mediated by central CRH receptors but not by melanocortin receptors-3/4 and that PrRP can modify Vo2.
D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage*; D001831:Body Temperature / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D007028:Hypothalamic Hormones / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009479:Neuropeptides / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D056690:Prolactin-Releasing Hormone; D051381:Rats; D017207:Rats, Sprague-Dawley; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors / Q000502:physiology; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D012528:Satiety Response
D001067:Appetite Depressants; D007028:Hypothalamic Hormones; D009479:Neuropeptides; D010446:Peptide Fragments; C534379:Prlh protein, rat; D056690:Prolactin-Releasing Hormone; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018019:Receptors, Corticotropin-Releasing Hormone; C103272:SHU 9119; C104416:astressin; D009074:Melanocyte-Stimulating Hormones; D003346:Corticotropin-Releasing Hormone