Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers

被引:351
作者
Lawrence, CB [1 ]
Snape, AC [1 ]
Baudoin, FMH [1 ]
Luckman, SM [1 ]
机构
[1] Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England
关键词
D O I
10.1210/en.143.1.155
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 demonthalamic 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.
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页码:155 / 162
页数:8
相关论文
共 43 条
[1]   Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin [J].
Asakawa, A ;
Inui, A ;
Kaga, T ;
Yuzuriha, H ;
Nagata, T ;
Ueno, N ;
Makino, S ;
Fujimiya, M ;
Niijima, A ;
Fujino, MA ;
Kasuga, M .
GASTROENTEROLOGY, 2001, 120 (02) :337-345
[2]  
Bailey ART, 2000, J NEUROENDOCRINOL, V12, P191
[3]   Central actions of the nonpeptide growth hormone secretagogue GHS-25 [J].
Bailey, ART ;
Gilliver, L ;
Leng, G ;
Smith, RG .
ENDOCRINE, 2001, 14 (01) :15-19
[4]   Hypothalamic growth hormone secretagogue-receptor (GHS-R) expression is regulated by growth hormone in the rat [J].
Bennett, PA ;
Thomas, GB ;
Howard, AD ;
Feighner, SD ;
VanderPloeg, LHT ;
Smith, RG ;
Robinson, ICAF .
ENDOCRINOLOGY, 1997, 138 (11) :4552-4557
[5]   Growth hormone-releasing peptide (GHRP) [J].
Bowers, CY .
CELLULAR AND MOLECULAR LIFE SCIENCES, 1998, 54 (12) :1316-1329
[6]   ON THE INVITRO AND INVIVO ACTIVITY OF A NEW SYNTHETIC HEXAPEPTIDE THAT ACTS ON THE PITUITARY TO SPECIFICALLY RELEASE GROWTH-HORMONE [J].
BOWERS, CY ;
MOMANY, FA ;
REYNOLDS, GA ;
HONG, A .
ENDOCRINOLOGY, 1984, 114 (05) :1537-1545
[7]  
Broberger C, 1998, J COMP NEUROL, V402, P460
[8]   Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats [J].
Date, Y ;
Murakami, N ;
Kojima, M ;
Kuroiwa, T ;
Matsukura, S ;
Kangawa, K ;
Nakazato, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 275 (02) :477-480
[9]   Ghrelin acts in the central nervous system to stimulate gastric acid secretion [J].
Date, Y ;
Nakazato, M ;
Murakami, N ;
Kojima, M ;
Kangawa, K ;
Matsukura, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 280 (03) :904-907
[10]   CENTRAL ACTIONS OF PEPTIDE AND NONPEPTIDE GROWTH-HORMONE SECRETAGOGUES IN THE RAT [J].
DICKSON, SL ;
LENG, G ;
DYBALL, REJ ;
SMITH, RG .
NEUROENDOCRINOLOGY, 1995, 61 (01) :36-43