κ-opioid receptor agonist suppression of HIV-1 expression in CD4+ lymphocytes

Phillip K. Peterson, Genya Gekker, James R. Lokensgard, Jean M. Bidlack, An Chih Chang, Xingin Fang, Philip S. Portoghese

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Synthetic κ-opioid receptor (KOR) agonists have been shown to suppress HIV-1 expression in acutely infected macrophages. In the present study, we examined the effects of the KOR ligand trans-3,4-dichloro-N-methyl-N[2-(1-pyrolidinyl)cyclohexyl]benzeneaceamide methanesulfonate (U50,488) on HIV-1 expression in CD4+ lymphocytes, the main target cell of this virus. When U50,488 was added to activated CD4+ lymphocytes, HIV-1 expression was inhibited in a concentration- and time-dependent manner with maximal suppression (≈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 acting via a KOR-related mechanism. Support for the involvement of KOR was provided 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 include cells outside of the nervous system and suggest a potential role for these agents in the treatment of HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)1145-1151
Number of pages7
JournalBiochemical Pharmacology
Volume61
Issue number9
DOIs
StatePublished - May 1 2001

Bibliographical note

Funding Information:
This work was supported, in part, by U.S. Public Health Service Grants DA09924, DA01533, K05-DA 00360, and DA04355.

Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.

Keywords

  • AIDS
  • CD4 lymphocytes
  • HIV
  • Opioids
  • U50,488
  • κ-opioid receptor ligands

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