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 language | English (US) |
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Pages (from-to) | 273-278 |
Number of pages | 6 |
Journal | Neuropharmacology |
Volume | 38 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1999 |
Bibliographical note
Funding Information:This research was supported by USPHS grants DA-04381, DA-09924, and DA-01533. We are grateful to Fred Kravtiz for his invaluable input and to Kris Sherer for assistance in manuscript preparation.
Keywords
- Endogenous opioid peptides
- Endomorphin
- Human immunodeficiency virus
- Neuroimmunomodulation
- μ-opioid receptors