Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting

Regul Pept. 2003 Mar 28;111(1-3):161-7. doi: 10.1016/s0167-0115(02)00283-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Dose-Response Relationship, Drug
  • Eating / physiology
  • Fasting / metabolism*
  • Ghrelin
  • Growth Hormone-Releasing Hormone / antagonists & inhibitors
  • Immunoglobulin G / pharmacology
  • Injections, Intraventricular
  • Male
  • Microinjections
  • Neuropeptide Y / antagonists & inhibitors
  • Peptide Hormones / immunology
  • Peptide Hormones / pharmacology*
  • Peptide Hormones / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Sermorelin / analogs & derivatives*
  • Sermorelin / pharmacology


  • Ghrelin
  • Immunoglobulin G
  • MZ 4-71
  • Neuropeptide Y
  • Peptide Hormones
  • Receptors, Neuropeptide
  • Sermorelin
  • Growth Hormone-Releasing Hormone