Cell-specific actions of HIV-Tat and morphine on opioid receptor expression in glia.
HIV-1 patients who abuse opiate-based drugs, including heroin and morphine, are at a higher risk of developing HIV dementia. The effects of opiates are mediated predominantly through opioid receptors, which are expressed on glial cells. As HIV-1 infection in the CNS is restricted to glial cells, experiments were designed to measure the cell-specific effects of HIV Tat and morphine exposure on opioid receptor expression in both astrocytes and microglia. Specifically, the cell-type-specific pattern of mu opioid receptor (MOR), delta opioid receptor (DOR), and kappa opioid receptor (KOR) localization (surface vs. intracellular) and expression of opioid receptor mRNA were determined after exposure to morphine in the presence and the absence of Tat in primary cultured microglia and astrocytes. Data show that morphine treatment caused significantly decreased cell surface expression of opioid receptors in microglia but not in astrocytes. However, morphine treatment in the presence of Tat significantly increased intracellular expression of opioid receptors and prevented morphine-induced cell surface opioid receptor down-regulation in microglia. These findings document that cell surface opioid receptor expression is divergently regulated by morphine in microglia compared with in astrocytes, and further suggest that HIV-Tat could exacerbate opioid receptor signaling in microglia by increasing receptor expression and/or altering ligand-induced trafficking of opioid receptors.
Turchan-Cholewo
Jadwiga
J
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA.
Dimayuga
Filomena O
FO
Ding
Qunxing
Q
Keller
Jeffrey N
JN
Hauser
Kurt F
KF
Knapp
Pamela E
PE
Bruce-Keller
Annadora J
AJ
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; C512124:HIV-TAT-survivin (T34A) protein; D011957:Receptors, Opioid; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus; D009020:Morphine