The GHS-R Blocker D-[Lys3] GHRP-6 Serves as CCR5 Chemokine Receptor Antagonist

@article{Patel2012TheGB,
  title={The GHS-R Blocker D-[Lys3] GHRP-6 Serves as CCR5 Chemokine Receptor Antagonist},
  author={Kalpesh Patel and Vishwa Deep Dixit and Jun Ho Lee and Jie-Wan Kim and Eric M. Schaffer and Dzung H. Nguyen and Dennis D. Taub},
  journal={International Journal of Medical Sciences},
  year={2012},
  volume={9},
  pages={51 - 58}
}
[D-Lys3]-Growth Hormone Releasing Peptide-6 (DLS) is widely utilized in vivo and in vitro as a selective ghrelin receptor (GHS-R) antagonist. This antagonist is one of the most common antagonists utilized in vivo to block GHS-R function and activity. Here, we found that DLS also has the ability to modestly block chemokine function and ligand binding to the chemokine receptor CCR5. The DLS effects on RANTES binding and Erk signaling as well as calcium mobilization appears to be much stronger… 

Figures from this paper

[D-Lys3]-GHRP-6 exhibits pro-autophagic effects on skeletal muscle
Limited short-term effects on human prostate cancer xenograft growth and epidermal growth factor receptor gene expression by the ghrelin receptor antagonist [D-Lys3]-GHRP-6
TLDR
Daily treatment with the ghrelin receptor antagonist [D-Lys3]-GHRP-6 has transitory effects on prostate xenograft tumours in mice, which rapidly develop an apparent resistance to the antagonist.
Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin and LEAP2, in a 4‐day binge eating model
TLDR
Current data indicate that GHSR activity in the brain affects binge‐like HF intake in mice independently of plasma levels of ghrelin and LEAP2.
Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
TLDR
Because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions.
Pharmacological characterization of the first in class clinical candidate PF‐05190457: a selective ghrelin receptor competitive antagonist with inverse agonism that increases vagal afferent firing and glucose‐dependent insulin secretion ex vivo
TLDR
The aim was to pharmacologically characterize the novel small‐molecule antagonist PF‐05190457 and assess translational pharmacology ex vivo and determine its application in the treatment of obesity and type 2 diabetes.
CHEMOKINE RECEPTORS IN HIV INFECTION
TLDR
The role of various chemokines receptors in the infection of HIV and the various aspects of future strategies to inhibit the HIV infection are highlighted.
Desacyl ghrelin prevents doxorubicin-induced myocardial fibrosis and apoptosis via the GHSR-independent pathway.
TLDR
It is demonstrated clearly that desacyl ghrelin protects the cardiomyocytes against the doxorubicin-inducedCardiomyopathy by preventing the activation of cardiac fibrosis and apoptosis, and the effects are probably mediated through GHSR-independent mechanism.
Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds
TLDR
Evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic.
The function and mechanisms of action of ghrelin and obestatin in ovarian cancer
TLDR
It is demonstrated for the first time that both ghrelin and obestatin increase cell migration in ovarian cancer cell lines and may play a role in cancer progression.
...
...

References

SHOWING 1-10 OF 22 REFERENCES
Development of growth hormone secretagogues.
TLDR
The GH secretagogues act through all four mechanisms to reproduce a young adult physiological GH profile in elderly subjects that was accompanied by increased bone mineral density and lean mass, modest improvements in strength, and improved recovery from hip fracture.
Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.
TLDR
This is the first report demonstrating that ghrelin functions as a key signal, coupling the metabolic axis to the immune system, and supporting the potential use of gh Relin and GHS-R agonists in the management of disease-associated cachexia.
A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity.
  • M. Baba, O. Nishimura, M. Fujino
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
TAK-779 displayed highly potent and selective inhibition of R5 HIV-1 replication without showing any cytotoxicity to the host cells, and the inhibition of beta-chemokine receptors appeared to be specific to CCR5.
Ghrelin: structure and function.
TLDR
The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by gh Relin derived from the stomach, which plays important roles for maintaining GH release and energy homeostasis in vertebrates.
The chemokine/chemokine-receptor family: potential and progress for therapeutic intervention.
Cholesterol is essential for macrophage inflammatory protein 1 beta binding and conformational integrity of CC chemokine receptor 5.
TLDR
It is found that cholesterol extraction by hydroxypropyl-beta-cyclodextrin (BCD) significantly reduced the binding and signaling of macrophage inflammatory protein 1 beta (MIP-1 beta) using CCR5-expressing CEM-NKR T cells, demonstrating that cholesterol and lipid rafts are important for the maintenance of the C CR5 conformation and are necessary for both the binding of this chemokine receptor.
A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone Release
TLDR
A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs.
Antagonism of ghrelin receptor reduces food intake and body weight gain in mice
TLDR
Gastric peptide ghrelin and GHS-R may be promising therapeutic targets not only for anorexia-cachexia but also for obesity and type 2 diabetes, which are becoming increasingly prevalent worldwide.
AIDS-related insulin resistance and lipodystrophy syndrome.
  • T. Kino, G. Chrousos
  • Medicine, Biology
    Current drug targets. Immune, endocrine and metabolic disorders
  • 2003
TLDR
The current understanding of the pathogenesis and therapeutic approach of this newly emerging AIDS-associated metabolic syndrome, which is observed in 30-80% of AIDS patients who are well controlled by HAART is reviewed.
The appealing story of HIV entry inhibitors : from discovery of biological mechanisms to drug development.
TLDR
The story of the first of these drugs, enfuvirtide, which has successfully completed phase III clinical trials, has been approved by the US FDA and by the European Medicines Agency, and is now commercially available worldwide, is an example of how the knowledge of basic molecular mechanisms can rapidly translate into the development of clinically effective molecules.
...
...