Int J Med Sci 2012; 9(1):51-58. doi:10.7150/ijms.9.51 This issue

Research Paper

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

Kalpesh Patel, Vishwa Deep Dixit, Jun Ho Lee, Jie Wan Kim, Eric M. Schaffer*, Dzung Nguyen#, Dennis D. Taub

Laboratory of Molecular Biology and Immunology, National Institute on Aging, Intramural Program, NIH, 251 Bayview Boulevard, Baltimore, MD. 21224, USA.
Present Address: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD. 21231.
Present Address: Laboratory of Neuroendocrine-Immunology, Pennington Biomedical Research Center, LSU System, Baton Rouge LA. 70808.
* Present Address: BioSensors Branch, RDCB-DRB-S, Edgewood Chemical Biological Center, APGEA, MD. 21010.
# Present Address: BioLegend, 1180 Roselle St., San Diego, CA. 92121.

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Patel K, Dixit VD, Lee JH, Kim JW, Schaffer EM, Nguyen D, Taub DD. The GHS-R Blocker D-[Lys3] GHRP-6 Serves as CCR5 Chemokine Receptor Antagonist. Int J Med Sci 2012; 9(1):51-58. doi:10.7150/ijms.9.51. Available from

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[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 than its effects on MIP-1α and MIP-1β. CCR5 have been shown to act as major co-receptor for HIV-1 entry into the CD4 positive host cells. To this end, we also found that DLS blocks M-tropic HIV-1 propagation in activated human PBMCs. These data demonstrate that DLS may not be a highly selective GHS-R1a inhibitor and may also effects on other G-protein coupled receptor (GPCR) family members. Moreover, DLS may have some potential clinical applications in blocking HIV infectivity and CCR5-mediated migration and function in various inflammatory disease states.

Keywords: MIP-1α, MIP-1β, RANTES, CCR5, HIV-1, Ghrelin, GHRP-6, GHS-R1a, Inflammation, Cancer.