Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers.
Ghrelin was recently identified as the endogenous ligand for the GH secretagogue (GHS) receptor. Like the synthetic GHSs [e.g. GH-releasing peptide-6 (GHRP-6)], ghrelin stimulates feeding and increases body weight in rats. The aim of this study was to identify brain regions that are activated by GHSs and determine whether the responses observed were secondary to food intake. In addition, possible mediators of GHS actions were examined. Intracerebroventricular (icv) injection of ghrelin or GHRP-6 into rats significantly stimulated food intake and transiently reduced core body temperature. The effect of both ghrelin and GHRP-6 on food intake was blocked by preadministration of a Y1 NPY receptor antagonist (BIBO3304). Using c-Fos immunohistochemistry, we demonstrated that icv ghrelin or GHRP-6 activated several hypothalamic brain regions, including the arcuate nucleus, paraventricular nucleus, dorsomedial nucleus, lateral hypothalamus, and two regions of the brainstem, the nucleus of the tractus solitarius and the area postrema. The cell activation induced by GHRP-6 was independent of food intake, as the same pattern and extent of c-Fos expression were observed in animals that were denied access to food following treatment. Finally, double immunohistochemistry indicated that orexin-containing, but not melanin-concentrating hormone-containing, neurons in the lateral hypothalamus were activated significantly by central administration of GHRP-6.
Lawrence
Catherine B
CB
University of Manchester School of Biological Sciences, Oxford Road, Manchester, United Kingdom M13 9PT.
Snape
Amelie C
AC
Baudoin
Florence M-H
FM
Luckman
Simon M
SM
D000818:Animals; D001066:Appetite / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors; D009479:Neuropeptides / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D000068797:Orexins; D036361:Peptide Hormones; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D009842:Oligopeptides; D000068797:Orexins; D036361:Peptide Hormones; D010455:Peptides; D016760:Proto-Oncogene Proteins c-fos; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D001120:Arginine; C117416:BIBO 3304