Growth Hormone Secretagogues

Isidro, Maria; Cordido, Fernando

doi:10.2174/138620706776055458

Cited by 8 publications

(9 citation statements)

References 31 publications

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“…Most recently, shorter peptides derived from D -Arg 1 - D -Phe 5 - D -Trp 7,9 -Leu 11 -substance P were shown to display inverse agonist activity on GHS-R1a as well [131]. Finally, GHS-R1a antagonists are also available, such as D -Lys 3 -GHRP-6, L765-867 [6, 7, 120], isoxazole, diaminopyrimidine and triazole derivatives [132,133,134]. Antibodies and RNA-Spiegelmers have been also developed for the blockade of GHS-R1a activity [135, 136].…”

Section: Type 1a Ghs Receptormentioning

confidence: 99%

“…Accordingly, it was hypothesized that the GH-releasing effect of the D -Trp 2 GHRP reflected the activity of an unknown endogenous factor or hypophysiotropic hormone distinct from growth hormone-releasing hormone (GHRH). The ability of the hexapeptide GHRP-6 to synergize with GHRH with remarkable potency in men [3], prompted the development of other GHRP-6 analogs (GHRP-1, GHRP-2 and hexarelin) with high potency [4,5,6] and some orally active peptido-mimetic GH secretagogues (GHS) such as the spiroperidine derivative MK-0677 [7,8,9,10,11,12]. Particularly remarkable is the broad range of chemistries of the GHS developed in the last few years by several pharmaceutical groups.…”

Section: Introductionmentioning

confidence: 99%

“…Particularly remarkable is the broad range of chemistries of the GHS developed in the last few years by several pharmaceutical groups. They consist of low-molecular-weight peptides, partial peptides and non-peptide molecules [6,13,14,15]. Several GHRP/GHS candidates were studied clinically, but none have reached the market [6, 11, 12].…”

Section: Introductionmentioning

confidence: 99%

“…They consist of low-molecular-weight peptides, partial peptides and non-peptide molecules [6,13,14,15]. Several GHRP/GHS candidates were studied clinically, but none have reached the market [6, 11, 12]. GHS bind to specific sites in the rat forebrain [16] and other brain regions such as the cerebral cortex, hippocampus, medulla oblongata and choroid plexus, although the greatest density of binding sites is in the hypothalamus and pituitary gland [17,18,19,20].…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneity of Ghrelin/Growth Hormone Secretagogue Receptors

Muccioli¹,

Baragli²,

Granata³

et al. 2007

Neuroendocrinology

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Ghrelin is a gastric polypeptide displaying strong GH-releasing activity by activation of the type 1a GH secretagogue receptor (GHS-R1a) located in the hypothalamus-pituitary axis. GHS-R1a is a G-protein-coupled receptor that, upon the binding of ghrelin or synthetic peptidyl and non-peptidyl ghrelin-mimetic agents known as GHS, preferentially couples to G_q, ultimately leading to increased intracellular calcium content. Beside the potent GH-releasing action, ghrelin and GHS influence food intake, gut motility, sleep, memory and behavior, glucose and lipid metabolism, cardiovascular performances, cell proliferation, immunological responses and reproduction. A growing body of evidence suggests that the cloned GHS-R1a alone cannot be the responsible for all these effects. The cloned GHS-R1b splice variant is apparently non-ghrelin/GHS-responsive, despite demonstration of expression in neoplastic tissues responsive to ghrelin not expressing GHS-R1a; GHS-R1a homologues sensitive to ghrelin are capable of interaction with GHS-R1b, forming heterodimeric species. Furthermore, GHS-R1a-deficient mice do not show evident abnormalities in growth and diet-induced obesity, suggesting the involvement of another receptor. Additional evidence of the existence of another receptor is that ghrelin and GHS do not always share the same biological activities and activate a variety of intracellular signalling systems besides G_q. The biological actions on the heart, adipose tissue, pancreas, cancer cells and brain shared by ghrelin and the non-acylated form of ghrelin (des-octanoyl ghrelin), which does not bind GHS-R1a, represent the best evidence for the existence of a still unknown, functionally active binding site for this family of molecules. Finally, located in the heart and blood vessels is the scavenger receptor CD36, involved in the endocytosis of the pro-atherogenic oxidized low-density lipoproteins, which is a pharmacologically and structurally distinct receptor for peptidyl GHS and not for ghrelin. This review highlights the most recently discovered features of GHS-R1a and the emerging evidence for a novel group of receptors that are not of the GHS1a type; these appear involved in the transduction of the multiple levels of information provided by GHS and ghrelin.

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Section: Type 1a Ghs Receptormentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heterogeneity of Ghrelin/Growth Hormone Secretagogue Receptors

Muccioli¹,

Baragli²,

Granata³

et al. 2007

Neuroendocrinology

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“…In 1976, it was revealed that modified opioid peptides had low GH secretory activity [2]. Since then, many efforts have been made to develop and improve potential applications of these GH secretagogues (GHSs) [3–7]. GHSs act on the pituitary and hypothalamus to release GH, not through the growth hormone releasing hormone receptor (GHRHR) but through an orphan receptor, the GHSR [8].…”

Section: Introductionmentioning

confidence: 99%

Effect of Ghrelin on Glucose-Insulin Homeostasis: Therapeutic Implications

Sangiao‐Alvarellos

Cordido

2010

International Journal of Peptides

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Ghrelin is a 28-amino-acid peptide that displays a strong growth hormone- (GH-) releasing activity through the activation of the growth hormone secretagogue receptor (GHSR). The first studies about role of ghrelin were focused on its orexigenic ability, but despite indisputable pharmacological data, the evidence for a physiological role for ghrelin in the control of appetite is much less clear. Mice with targeted deletion of either ghrelin or the GHSR exhibit an essentially normal metabolic phenotype when fed a regular chow diet, suggesting that ghrelin may have a redundant role in the regulation of food intake. RNAs for ghrelin as well as GHSR are expressed in the pancreas of rats and humans and several studies propose that ghrelin could have an important function in glucose homeostasis and insulin release, independent of GH secretion. Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin. For this reason, at least theoretically, ghrelin and/or its signalling manipulation could be useful for the treatment or prevention of diseases of glucose homeostasis such as type 2 diabetes.

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Abuse of Growth Hormone Among Young Athletes

Buzzini¹

2007

Pediatric Clinics of North America

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Growth Hormone Secretagogues

Cited by 8 publications

References 31 publications

Heterogeneity of Ghrelin/Growth Hormone Secretagogue Receptors

Heterogeneity of Ghrelin/Growth Hormone Secretagogue Receptors

Effect of Ghrelin on Glucose-Insulin Homeostasis: Therapeutic Implications

Abuse of Growth Hormone Among Young Athletes

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