Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures: implication of an atypical mu-opioid receptor.
Endogneous delta and kappa 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 approximately equal 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.
Peterson
P K
PK
Institute for Brain and Immune Disorders, Minneapolis Medical Research Foundation, MN 55404, USA. peter137@maroon.tc.umn.ed
Gekker
G
G
Hu
S
S
Lokensgard
J
J
Portoghese
P S
PS
Chao
C C
CC
D000701:Analgesics, Opioid / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005333:Fetus; D016655:HIV Core Protein p24 / Q000032:analysis / Q000096:biosynthesis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D017628:Microglia / Q000187:drug effects / Q000502:physiology / Q000821:virology*; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology* / Q000821:virology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000821:virology*; D009842:Oligopeptides / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D014779:Virus Replication / Q000187:drug effects*
D000701:Analgesics, Opioid; D004745:Enkephalins; D016655:HIV Core Protein p24; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C105294:endomorphin 2