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.
Rock
R Bryan
RB
Center for Infectious Diseases and Microbiology Translational Research and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Gekker
Genya
G
Hu
Shuxian
S
Sheng
Wen S
WS
Cabral
Guy A
GA
Martin
Billy R
BR
Peterson
Phillip K
PK
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