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) |
|---|---|
| Pages (from-to) | 273-278 |
| Number of pages | 6 |
| Journal | Neuropharmacology |
| Volume | 38 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 1999 |
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Keywords
- Endogenous opioid peptides
- Endomorphin
- Human immunodeficiency virus
- Neuroimmunomodulation
- μ-opioid receptors
Cite this
Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures : Implication of an atypical μ-opoid receptor. / Peterson, Phillip K.; Gekker, Genya; Hu, Shuxian; Lokensgard, James R; Portoghese, Philip S; Chao, Chun C.
In: Neuropharmacology, Vol. 38, No. 2, 01.02.1999, p. 273-278.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures
T2 - Implication of an atypical μ-opoid receptor
AU - Peterson, Phillip K.
AU - Gekker, Genya
AU - Hu, Shuxian
AU - Lokensgard, James R
AU - Portoghese, Philip S
AU - Chao, Chun C.
PY - 1999/2/1
Y1 - 1999/2/1
N2 - 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.
AB - 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.
KW - Endogenous opioid peptides
KW - Endomorphin
KW - Human immunodeficiency virus
KW - Neuroimmunomodulation
KW - μ-opioid receptors
UR - http://www.scopus.com/inward/record.url?scp=0032968784&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032968784&partnerID=8YFLogxK
U2 - 10.1016/S0028-3908(98)00167-1
DO - 10.1016/S0028-3908(98)00167-1
M3 - Article
VL - 38
SP - 273
EP - 278
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 2
ER -