We previously examined the expression of specific C-terminal μ-opioid receptor (MOR) splice variants in human central nervous system cell types and HIV-infected brain tissue from individuals with neurocognitive impairment ± HIV encephalitis (HIVE). In the present study, we examined the N-terminal splice variant MOR-1K, which mediates excitatory cellular signaling.
We found segregation of expression ranging from undetectable to seemingly exclusive across nervous system cell types compared to the pool of C-terminal MOR splice variants using the real-time polymerase chain reaction (RT-PCR). Expression of MOR-1K mRNA was also increased in HIV-infected individuals with combined neurocognitive impairment and HIVE compared with the other groups. MOR-1K expression correlated with the level of patient neurocognitive impairment, whereas the pool of C-terminal MOR splice variants did not. HIVE was also associated with increased expression of the inflammatory mediators MCP-1, MCP-2, and RANTES, but not the host HIV coreceptors CXCR4 and CCR5 or the CD4 receptor using qRT-PCR. Network analysis of microarray data from these same patients revealed filamin A (FLNA) as a possible interaction partner with MOR-1K, and FLNA gene expression was also found to be upregulated in HIVE using qRT-PCR. Overexpression of FLNA in HEK293 cells redistributed MOR-1K from intracellular compartments to the cell surface.
These results suggest that HIVE, and neurocognitive impairment depending on its severity, are associated with enhanced MOR-1K signaling through both increased expression and trafficking to the cell surface, which may alter the contribution of MOR receptor isoforms and exacerbate the effects of MOR activation in neuroAIDS.
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aDepartment of Pharmacology & Toxicology
bDepartment of Anatomy & Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
cCenter for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
dDepartment of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy
eInstitute for Drug & Alcohol Studies, Virginia Commonwealth University, Richmond, Virginia, USA.
Correspondence to Kurt F. Hauser, PhD, Department of Pharmacology & Toxicology, Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Room 439, Kontos Medical Sciences Building, 1217 East Marshall Street, Richmond, VA 23298-0613, USA. Tel: +1 804 628 7579; fax: +1 804 827 9974; e-mail: email@example.com
Received 20 June, 2013
Revised 10 October, 2013
Accepted 10 October, 2013
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