Evidence for a role of the GHS-R1a receptors in ghrelin inhibition of gastric acid secretion in the rat.
J Neuroendocrinol
; 18(2): 122-8, 2006 Feb.
Article
em En
| MEDLINE
| ID: mdl-16420281
ABSTRACT
Ghrelin, the endogenous ligand of the GH secretagogue receptor (GHS-R) has been previously shown to inhibit gastric acid secretion in pylorus-ligated rats. Two isoforms of GHS-R have been identified GHS-R(1a) and GHS-R(1b). The present study aimed (i) to characterise the type of GHS-R involved in the central gastric inhibitory activity of ghrelin by using des-octanoyl ghrelin, and synthetic GHS-R(1a) agonist (EP1572) and antagonist (D-Lys(3)-GHRP-6) and (ii) to investigate the relationship between ghrelin and cortistatin (CST) in the control of gastric acid secretion by using the natural neuropeptide CST-14 and the synthetic octapeptide CST-8. The specific interactions of all the compounds with GHS-R(1a) were determined by comparing their ability to displace labelled ghrelin or somatostatin from its receptors on rat hypothalamic membranes or on rat cardiomyocyte, respectively. Intracerebroventricular administration of 0.01 and 1 nmol/rat des-octanoyl ghrelin did not affect gastric acid secretion in pylorus-ligated rats, whereas EP1572 either i.c.v. (0.01-1 nmol/rat) or i.p. (10 and 20 nmol/kg) inhibited acid gastric secretion. Preteatment with D-Lys(3)GHRP-6 (3 nmol/rat, i.c.v.) was able to remove the inhibitory action of ghrelin (0.01 nmol/rat, i.c.v.) on gastric acid volume and acid output, thus indicating that the type 1a GHS-R likely mediates the gastric inhibitory action of ghrelin. This is supported by binding data showing that D-Lys(3)GHRP-6, but not des-octanoyl ghrelin, binds to hypothalamic GHS-R. CST-14 (1 nmol/rat, i.c.v.) did not affect either basal or ghrelin inhibition of gastric acid secretion. CST-8 (1 nmol/rat, i.c.v.) was able to counteract the gastric ghrelin response. The observation that CST-14 binds both GHR-S and somatostatin receptors, whereas CST-8 specifically displaces only ghrelin binding, indicates that CST-8 behaves as a GHS-R(1a) antagonist.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Receptores de Somatostatina
/
Hormônios Peptídicos
/
Receptores Acoplados a Proteínas G
/
Ácido Gástrico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neuroendocrinol
Assunto da revista:
ENDOCRINOLOGIA
/
NEUROLOGIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Itália