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.
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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