Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting.
Ghrelin, a circulating growth-hormone releasing peptide derived from stomach, stimulates food intake through neuropeptide Y (NPY) neurons of the arcuate nucleus in the hypothalamus (ARC). We examined the effect of ghrelin microinjected into the ARC and the influence of intracerebroventricular (i.c.v.) pretreatment with a GHRH or NPY receptor antagonist on ghrelin-induced food intake in free-feeding male rats. Ghrelin (0.1-1 microg) stimulated food intake in a dose-dependent manner, and this effect was reduced by 55-60% by the Y(5) NPY receptor antagonist (10 microg i.c.v.), but not by the GHRH receptor antagonist MZ-4-71 (10 microg i.c.v.). We also evaluated the effects of passive ghrelin immunoneutralization by the microinjection of anti-ghrelin immunoglobulins (IgGs) intracerebroventricularly or directly into the ARC on food intake in free-feeding and fasted male rats. i.c.v. administration of anti-ghrelin IgGs decreased cumulative food intake over 24 h, whereas microinfusion of anti-ghrelin IgGs into the ARC induced only a short-lived (2 and 6 h) effect. Collectively, these data would indicate that centrally derived ghrelin has a major role in the control of food intake in rats and, in this context, blood-born ghrelin would be effective only in relation to its ability to reach the ARC, which is devoid of blood-brain barrier.
Bagnasco
Michela
M
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli, 32-20129 Milan, Italy.
Tulipano
Giovanni
G
Melis
Maria R
MR
Argiolas
Antonio
A
Cocchi
Daniela
D
Muller
Eugenio E
EE
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000378:metabolism*; D054439:Ghrelin; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors; D007074:Immunoglobulin G / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors; D036361:Peptide Hormones / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors; D017337:Sermorelin / Q000031:analogs & derivatives* / Q000494:pharmacology
D054439:Ghrelin; D007074:Immunoglobulin G; C095215:MZ 4-71; D009478:Neuropeptide Y; D036361:Peptide Hormones; D018013:Receptors, Neuropeptide; D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone