Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures:: implication of an atypical μ-opioid receptor

被引:54
作者
Peterson, PK [1 ]
Gekker, G
Hu, SX
Lokensgard, J
Portoghese, PS
Chao, CC
机构
[1] Minneapolis Med Res Fdn, Inst Brain & Immune Disorders, Minneapolis, MN 55404 USA
[2] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Coll Pharm, Dept Med Chem, Minneapolis, MN 55455 USA
关键词
endomorphin; endogenous opioid peptides; mu-opioid receptors; human immunodeficiency virus; neuroimmunomodulation;
D O I
10.1016/S0028-3908(98)00167-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Endogneous delta and re opioid peptides possess a variety of immunomodulatory properties, and kappa-opioid receptor ligands recently were shown to suppress the expression of human immunodeficiency virus type 1 (HIV-1) in microglial cells, the resident macrophages of the brain. To determine whether the newly discovered endogenous mu-opioid receptor ligands endomorphin-1 and -2 would affect HIV-1 replication, these peptides were added to acutely infected brain cell cultures. Endomorphin-1 potentiated viral expression, in a bell-shaped dose-response manner with maximal enhancement congruent to 35% at 10(-10) M, in both mixed glial/neuronal cell and purified microglial cell cultures. Endomorphin-1's amplifying effect was blocked by pretreatment of brain cells with either the mu-opioid receptor selective antagonist beta-funaltrexamine or the G protein inhibitor pertussis toxin. However, the classical mu receptor agonists morphine and DAMGO (Tyr-d-Ala-Gly-N-Me-Phe-Gly-ol) had no effect on viral expression or on endomorphin-1's amplifying effect. Taken together, these findings suggest that in this in vitro model of HIV-1 brain infection, endomorphin-1 potentiates viral expression via activation of an atypical mu-selective opioid receptor. They also provide evidence, for the first time, that an endogenous mu-opioid peptide has neuroimmunomodulatory activity. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:273 / 278
页数:6
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