kappa-opioid receptor agonist suppression of HIV-1 expression in CD4(+) lymphocytes

Citation
Pk. Peterson et al., kappa-opioid receptor agonist suppression of HIV-1 expression in CD4(+) lymphocytes, BIOCH PHARM, 61(9), 2001, pp. 1145-1151
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
61
Issue
9
Year of publication
2001
Pages
1145 - 1151
Database
ISI
SICI code
0006-2952(20010501)61:9<1145:KRASOH>2.0.ZU;2-A
Abstract
Synthetic K-opioid receptor (KOR) agonists have been shown to suppress HIV- 1 expression in acutely infected macrophages. In the present study, we exam ined the effects of the KOR ligand trans-3,4-dichloro-N-methyl-N[2-(1 -pyro lidinyl)cyclohexyl] benzeneaceamide methanesulfonate (U50,488) on HIV-1 exp ression in CD4(+) lymphocytes, the main target cell of this virus. When U50 ,488 was added to activated CD4(+) lymphocytes, HIV-1 expression was inhibi ted in a concentration- and time-dependent manner with maximal suppression ( approximate to 60%) at 10(-7) M U50,488, The KOR selective antagonist nor -binaltorphimine (nor-BNI) had no effect by itself on viral expression but blocked the antiviral property of U50,488, suggesting that U50,488 was acti ng via a KOR-related mechanism. Support for the involvement of KOR was prov ided by the findings that 34% of activated CD4(+) lymphocytes were positive for KOR, using an immunofluorescence technique, and that seven additional synthetic KOR ligands also inhibited HIV-1 expression. The results of this study broaden understanding of the antiviral properties of KOR ligands to i nclude cells outside of the nervous system and suggest a potential role for these agents in the treatment of HIV-I infection. (C) 2001 Elsevier Scienc e Inc. All rights reserved.