Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
SPECIFIC RECEPTORS FOR SYNTHETIC GH SECRETAGOGUES IN THE HUMAN BRAIN AND PITUITARY-GLAND
Autore:
MUCCIOLI G; GHE C; GHIGO MC; PAPOTTI M; ARVAT E; BOGHEN MF; NILSSON MHL; DEGHENGHI R; ONG H; GHIGO E;
Indirizzi:
UNIV TURIN,DEPT ANAT PHARMACOL & FORENS MED,DIV PHARMACOL,VIA P GIURIA 13 I-10125 TURIN ITALY UNIV TURIN,DEPT BIOMED SCI & HUMAN ONCOL I-10125 TURIN ITALY UNIV TURIN,DEPT INTERNAL MED I-10125 TURIN ITALY PHARMACIA & UPJOHN INC STOCKHOLM SWEDEN EUROPEPTIDES ARGENTEUIL FRANCE UNIV MONTREAL,FAC PHARM MONTREAL PQ H3C 3J7 CANADA
Titolo Testata:
Journal of Endocrinology
fascicolo: 1, volume: 157, anno: 1998,
pagine: 99 - 106
SICI:
0022-0795(1998)157:1<99:SRFSGS>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
HORMONE-RELEASING PEPTIDE; PORCINE ANTERIOR-PITUITARY; GROWTH-HORMONE; HYPOTHALAMIC MEMBRANES; ARCUATE NUCLEUS; CELLS; RAT; HEXAPEPTIDE; HEXARELIN; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
G. Muccioli et al., "SPECIFIC RECEPTORS FOR SYNTHETIC GH SECRETAGOGUES IN THE HUMAN BRAIN AND PITUITARY-GLAND", Journal of Endocrinology, 157(1), 1998, pp. 99-106

Abstract

In vitro studies have been performed to demonstrate and characterize specific binding sites for synthetic GH secretagogues (sGHS) on membranes from pituitary gland and different human brain regions. A binding assay for sGHS was established using a peptidyl sGHS (Tyr-Ala-hexarelin) which had been radioiodinated to high specific activity at the Tyr residue. Specific binding sites for I-125-labelled Tyr-Ala-hexarelin were detected mainly in membranes isolated from pituitary gland and hypothalamus, but they were also present in other brain areas such as choroid plexus, cerebral cortex, hippocampus and medulla oblongata with no sex-related differences. In contrast, negligible binding was found in the thalamus, striatum, substantia nigra, cerebellum and corpus callosum. The binding of I-125-labelled Tyr-Ala-hexarelin to membrane-binding sites is a saturable and reversible process, depending on incubation time and pH of the buffer. Scatchard analysis of the binding revealed a finite number of binding sites in the hypothalamus and pituitary gland with a dissociation constant (K-d) of (1.5+/-0.3) x 10(-9) and (2.1+/-0.4) x 10(-9) mol/l respectively. Receptor activity is sensitiveto trypsin and phospholipase C digestion, suggesting that protein andphospholipids are essential for the binding of I-125-labelled Tyr-Ala-hexarelin. The binding of I-125-labelled Tyr-Ala-hexarelin to pituitary and hypothalamic membranes was displaced in a dose-dependent mannerby different unlabelled synthetic peptidyl (Tyr-Ala-hexarelin, GHRP2,hexarelin, GHRP6) and non-peptidyl (MK 0677) sGHS. An inhibition of the specific binding was also observed when binding was performed in the presence of [D-Arg(1)-D-Phe(5)-D-Trp(7,9)-Leu(11)]-substance P, a substance P antagonist that has been found to inhibit GH release in response to sGHS. In contrast, no competition was observed in the presenceof other neuropeptides (GHRH, somatostatin, galanin or Met-enkephalin) which have a known influence on GH release. In conclusion, the present data demonstrate that sGHS have specific receptors in human brain and pituitary gland and reinforce the hypothesis that these compounds could be the synthetic counterpart of an endogenous GH secretagogue involved in the neuroendocrine control of GH secretion and possibly in other central activities.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/08/20 alle ore 08:24:14