The GHS-R blocker D-[Lys3] GHRP-6 serves as CCR5 chemokine receptor antagonist.
[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.
Laboratory of Molecular Biology and Immunology, National Institute on Aging, Intramural Program, NIH, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
Kalpesh
K
Patel
Vishwa Deep
VD
Dixit
Jun Ho
JH
Lee
Jie Wan
JW
Kim
Eric M
EM
Schaffer
Dzung
D
Nguyen
Dennis D
DD
Taub
D016475:3T3 Cells; D000818:Animals; D065100:CCR5 Receptor Antagonists; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D054407:Chemokine CCL4 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism*; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000378:metabolism*; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
C515429:CCL3 protein, human; C066507:CCL4 protein, human; D065100:CCR5 Receptor Antagonists; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; C520836:GHRP-6, Lys(3)-; D008024:Ligands; D009842:Oligopeptides; D019713:Receptors, CCR5; D054440:Receptors, Ghrelin; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium