The melanocortins, not oxytocin, mediate the anorexigenic and antidipsogenic effects of neuronostatin.
Neuronostatin, a recently discovered peptide derived from the somatostatin preprohormone, significantly inhibited both food and water intake when administered centrally in adult male rats. Because neuronostatin is highly produced in the hypothalamus, an area of the brain through which important feeding circuits, including the central melanocortin system, communicate, we sought to determine if the anorexigenic and antidipsogenic effects of neuronostatin would be reversed by pretreatment with the melanocortin 3/4 receptor antagonist, SHU9119. SHU9119 pretreatment reversed the effect of neuronostatin on both food and water intake. We have shown recently that the central oxytocin system is a potential downstream mediator of the anorexignic action of alpha-MSH. We therefore tested whether the effects of neuronostatin also were dependent upon central oxytocin receptors. Neuronostatin-induced anorexia was not reversed by pretreatment with the oxytocin receptor antagonist, OVT, suggesting that neuronostatin acts through a unique subset of POMC neurons that do not signal via central oxytocin receptors.
Yosten
Gina L C
GL
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 S. Grand Boulevard, Saint Louis, MO 63104, USA. gyosten@slu.edu
Samson
Willis K
WK
D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology*; D004326:Drinking / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D053486:Melanocortins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010121:Oxytocin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology*; D036361:Peptide Hormones / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
D006727:Hormone Antagonists; D053486:Melanocortins; D010446:Peptide Fragments; D036361:Peptide Hormones; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018045:Receptors, Oxytocin; C554543:neuronostatin protein, rat; C103272:SHU 9119; D010121:Oxytocin; D013004:Somatostatin; C042951:oxytocin,1-(beta-mercapto-(beta, beta-cyclopentamethylene)propionic acid)-Tyr(OMe)(2)-Orn(8)-; D009074:Melanocyte-Stimulating Hormones