Morphine potentiates HIV-1 gp120-induced neuronal apoptosis.
To investigate the effect of opiates on human immunodeficiency virus type 1 (HIV-1)-related neuronal apoptosis, primary human fetal neuronal/glial cell cultures were exposed to gp120(IIIB) in the absence and the presence of morphine. Although morphine by itself had little effect on neuronal survival, the combination of morphine (>/=10(-7) mol/L) and gp120(IIIB) (1 nmol/L) significantly increased neuronal apoptosis. The mechanism whereby morphine potentiates gp120(IIIB)-induced neuronal apoptosis appears to involve activation of the p38 mitogen-activated protein kinase intracellular signaling pathway and microglial cells dispersed within the neuronal/glial cell cultures. These results provide additional insight into the molecular basis whereby opiate abuse could promote HIV-1-associated dementia.
Hu
Shuxian
S
Division of Infectious Diseases and International Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Sheng
Wen S
WS
Lokensgard
James R
JR
Peterson
Phillip K
PK
D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005333:Fetus; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D009294:Narcotics; D009020:Morphine; D048051:p38 Mitogen-Activated Protein Kinases