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

Phillip K. Peterson, Genya Gekker, Shuxian Hu, James R Lokensgard, Philip S Portoghese, Chun C. Chao

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Endogneous δ and κ opioid peptides possess a variety of immunomodulatory properties, and κ-opioid receptor ligands recently were shown to suppress the expression of human immunodeficiency virus type 1 (HIV-I) in microglial cells, the resident macrophages of the brain. To determine whether the newly discovered endogenous μ-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 ≃ 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 μ-opioid receptor selective antagonist β-funaltrexamine or the G protein inhibitor pertussis toxin. However, the classical μ 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 μ-selective opioid receptor. They also provide evidence, for the first time, that an endogenous μ-opioid peptide has neuroimmunomodulatory activity.

Original languageEnglish (US)
Pages (from-to)273-278
Number of pages6
JournalNeuropharmacology
Volume38
Issue number2
DOIs
StatePublished - Feb 1 1999

Keywords

  • Endogenous opioid peptides
  • Endomorphin
  • Human immunodeficiency virus
  • Neuroimmunomodulation
  • μ-opioid receptors

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