期刊
JOURNAL OF NEUROVIROLOGY
卷 18, 期 3, 页码 181-190出版社
SPRINGER
DOI: 10.1007/s13365-012-0096-z
关键词
MOR/OPRM1; Splice variant; HIV-1; Opiate drug abuse; Astroglia; Microglia
资金
- National Institutes of Health (NIH)-National Institute on Drug Abuse [T32 DA007027, R01 DA024461, R01 DA018633, K02 DA027374]
- National Institute of Neurological Disorders and Stroke [U01MH083501, R24MH59724, U01MH083507, R24NS45491, 5U01MH083500, NS38841, U01MH083506, R24MH59745, U01MH083545, N01MH32002]
- NIH through the National Institute of Mental Health
The mu-opioid receptor (MOR) is known to undergo extensive alternative splicing as numerous splice variants of MOR have been identified. However, the functional significance of MOR variants, as well as how splice variants other than MOR-1 might differentially regulate human immunodeficiency virus type-1 (HIV-1) pathogenesis in the central nervous system (CNS), or elsewhere, has largely been ignored. Our findings suggest that there are specific differences in the MOR variant expression profile among CNS cell types, and that the expression levels of these variants are differentially regulated by HIV-1. While MOR-1A mRNA was detected in astroglia, microglia, and neurons, MOR-1 and MOR-1X were only found in astroglia. Expression of the various forms of MOR along with the chimeric G protein qi5 in HEK-293T cells resulted in differences in calcium/NFAT signaling with morphine treatment, suggesting that MOR variant expression might underlie functional differences in MOR-effector coupling and intracellular signaling across different cell types. Furthermore, the data suggest that the expression of MOR-1 and other MOR variants may also be differentially regulated in the brains of HIV-infected subjects with varying levels of neurocognitive impairment. Overall, the results reveal an unexpected finding that MOR-1 may not be the predominant form of MOR expressed by some CNS cell types and that other splice variants of MOR-1, with possible differing functions, may contribute to the diversity of MOR-related processes in the CNS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据