Laboratory of Molecular Biology and Immunology, National Institute on Aging, Intramural Program, NIH, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
Int J Med Sci. 2012;9(1):51-8. doi: 10.7150/ijms.9.51. Epub 2011 Nov 18.
[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.
[D-Lys3]-生长激素释放肽-6（DLS）在体内和体外被广泛用作选择性胃饥饿素受体（GHS-R）拮抗剂。这种拮抗剂是体内最常用的拮抗剂之一，用于阻断 GHS-R 功能和活性。在这里，我们发现 DLS 还具有适度阻断趋化因子功能和配体与趋化因子受体 CCR5 结合的能力。DLS 对 RANTES 结合和 Erk 信号以及钙动员的影响似乎比其对 MIP-1α 和 MIP-1β 的影响要强得多。CCR5 已被证明是 HIV-1 进入 CD4 阳性宿主细胞的主要共受体。为此，我们还发现 DLS 可阻断活化的人 PBMC 中 M 嗜性 HIV-1 的增殖。这些数据表明，DLS 可能不是高度选择性的 GHS-R1a 抑制剂，也可能对其他 G 蛋白偶联受体（GPCR）家族成员产生影响。此外，DLS 可能在阻断 HIV 感染性以及 CCR5 介导的迁移和各种炎症疾病状态中的功能方面具有一些潜在的临床应用。
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