Binding of a growth hormone releasing hexapeptide to specific hypothalamic and pituitary binding sites

Codd, Ellen E.; Shu, Arthur Y. L.; Walker, Richard F.

doi:10.1016/0028-3908(89)90129-9

Cited by 162 publications

(54 citation statements)

References 9 publications

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“…Binding studies 125 I-Labelled Tyr-Ala-hexarelin-binding studies were performed as previously described by Codd et al (1989). For single point binding assay, tissue membranes (corresponding to 100 µg protein) were incubated in triplicate at 0 C for 60 min with approximately 0·5 10 9 mol/l 125 I-labelled Tyr-Ala-hexarelin in a final volume of 0·5 ml assay buffer (50 mmol/l Tris, 2 mmol/l EGTA, 0·1% BSA, 0·03% bacitracin, titrated with HCl to pH 7·3).…”

Section: Membrane Preparationmentioning

confidence: 99%

Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland

Muccioli

Ghè²,

Ghigo³

et al. 1998

Journal of Endocrinology

143

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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 125 I-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 125 I-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) 10 9 and (2·1 0·4) 10 9 mol/l respectively. Receptor activity is sensitive to trypsin and phospholipase C digestion, suggesting that protein and phospholipids are essential for the binding of 125 I-labelled Tyr-Ala-hexarelin. The binding of 125 Ilabelled Tyr-Ala-hexarelin to pituitary and hypothalamic membranes was displaced in a dose-dependent manner by 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 [-Arg 1 --Phe 5 --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 presence of 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.

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Section: Membrane Preparationmentioning

confidence: 99%

Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland

Muccioli

Ghè²,

Ghigo³

et al. 1998

Journal of Endocrinology

143

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“…GHRPs were designed and derived from enkephalin through computer-modeling techniques [9]. Nonopioid receptors for GHRP have been identified in the hypothalamus and pituitary [10]. A previous study has demonstrated that GHRP synergizes with GHRH to increase GH release from rat pituitary cells [11].…”

Section: Somatostatin Pituitary Cellmentioning

confidence: 99%

Effect of Growth Hormone (GH)-Releasing Peptide (GHRP) on the Release of GH from Cultured Anterior Pituitary Cells in Cattle.

1994

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“…Though synthetic and non-natural, GHRPs bind to specific receptors at the pituitary level as well as within the central nervous system (CNS), particularly in the hypothalamus, though GHRP binding at the hippocampal and the cortical level is remarkable (10)(11)(12). The GHRP receptor has recently been cloned and shows no significant homology with any other G-protein coupled receptor known so far (13).…”

Section: Introductionmentioning

confidence: 99%

The GH, prolactin, ACTH and cortisol responses to Hexarelin, a synthetic hexapeptide, undergo different age-related variations

Arvat

Ramunni

Bellone

et al. 1997

European Journal of Endocrinology

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Hexarelin (HEX) is a synthetic growth hormone-releasing peptide (GHRP) which acts on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release in an age-dependent manner. Like other GHRPs, HEX possesses also prolactin (PRL) and ACTH/cortisol-releasing activity, similar to that of human corticotropin-releasing hormone (hCRH). The mechanisms underlying the stimulatory effect of GHRPs on lactotrope and corticotrope secretion are even less clear and the influence of age on these endocrine activities of GHRPs is unknown. To clarify this point we studied the GH, PRL, ACTH and cortisol responses to the maximal effective dose of HEX (2.0 mg/kg i.v.) in: 12 prepubertal children (Pre-C, 8 male, 4 female, age 5.8-12

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Binding of a growth hormone releasing hexapeptide to specific hypothalamic and pituitary binding sites

Cited by 162 publications

References 9 publications

Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland

Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland

Effect of Growth Hormone (GH)-Releasing Peptide (GHRP) on the Release of GH from Cultured Anterior Pituitary Cells in Cattle.

The GH, prolactin, ACTH and cortisol responses to Hexarelin, a synthetic hexapeptide, undergo different age-related variations

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