WIN55,212-2-mediated inhibition of HIV-1 expression in microglial cells: involvement of cannabinoid receptors.
Cannabinoid receptors CB(1) and CB(2) are primarily expressed in cells of the nervous and immune systems, respectively. Recently, the synthetic CB(1)/CB(2) agonist WIN55,212-2 was found to suppress replication of HIV-1 in microglial cell cultures. The present study was undertaken to test the hypothesis that WIN55,212-2's antiviral effect is mediated via CB(2) receptors. By reverse transcription-polymerase chain reaction, microglia were found to express both CB(1) and CB(2) receptors. Using additional CB(1)/CB(2) receptor agonists and selective antagonists, we found that CB(2) receptors are involved in WIN55,212-2's antiviral activity and surprisingly that the CB(1) receptor-selective antagonist SR141716A behaved as an agonist in these brain macrophages.
Center for Infectious Diseases and Microbiology Translational Research and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
R Bryan
RB
Rock
Genya
G
Gekker
Shuxian
S
Hu
Wen S
WS
Sheng
Guy A
GA
Cabral
Billy R
BR
Martin
Phillip K
PK
Peterson
D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D048588:Benzoxazines / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000821:virology*; D009025:Morpholines / Q000378:metabolism / Q000494:pharmacology*; D009281:Naphthalenes / Q000378:metabolism / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000378:metabolism / Q000502:physiology*
D019380:Anti-HIV Agents; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone