Kappa-opioid receptor agonist inhibition of HIV-1 envelope glycoprotein-mediated membrane fusion and CXCR4 expression on CD4(+) lymphocytes

Biochemical Pharmacology
J LokensgardP K Peterson

Abstract

Our previous studies have shown that the suppressive effect of kappa-opioid receptor (KOR) ligand treatment on HIV-1(AT) (a T-tropic strain) expression in acutely infected CD4(+) lymphocytes is time-dependent. This finding implied that the inhibition observed following treatment with KOR agonists such as U50,488 (trans-3,4-dichloro-N-methyl-N[2-(1-pyrolidinyl)cyclohexyl]benzeneaceamide methanesulfonate) occurs at an early step in the viral replication cycle, perhaps as early as viral entry. In the present study, we examined the hypothesis that U50,488 treatment of CD4(+) lymphocytes inhibits HIV-1 envelope (Env) glycoprotein-mediated membrane fusion. We used a vaccinia virus-based assay to measure the effects of U50,488 treatment of CD4(+) lymphocytes on HIV-1 IIIB Env glycoprotein-mediated fusogenic activity, based on the cytoplasmic activation of a reporter gene. The results show that U50,488 inhibited Env-mediated cell fusion in a bell-shaped concentration-response manner with suppression ranging between 31 and 98% at concentrations of 10(-8) and 10(-10)M (N=9 experiments). U50,488 was also found to inhibit cell fusion when monitored in situ with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining. Blockade ...Continue Reading

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Citations

Aug 19, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Shuxian HuRobert Bryan Rock
Dec 31, 2003·Bioorganic & Medicinal Chemistry·Elisabeth GreinerKenner C Rice
Nov 13, 2003·Peptides·Richard J Bodnar, Maria M Hadjimarkou
Jun 5, 2003·Biochemical Pharmacology·Gang WeiChun Su Yuan
Mar 5, 2003·Trends in Immunology·Thomas J Rogers, Phillip K Peterson
Jan 22, 2005·Journal of Medicinal Chemistry·Thomas A MunroFeng Yan
Sep 10, 2004·American Journal of Therapeutics·Ricardo VallejoRamsun Benyamin
Jun 6, 2012·AIDS Research and Treatment·Pichili Vijaya Bhaskar ReddyMadhavan P N Nair
Feb 9, 2013·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Dmitri ProudnikovMary J Kreek
Aug 25, 2010·Journal of Veterinary Emergency and Critical Care·Adesola OdunayoAmy E DeClue
Jul 28, 2005·Journal of Ethnopharmacology·Genya GekkerPhillip K Peterson
Jul 26, 2016·Frontiers in Microbiology·Alireza TahamtanVahid Salimi
Jan 26, 2006·Pharmacology, Biochemistry, and Behavior·Christopher R McCurdyMarcelo J Nieto
Aug 5, 2009·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·J FichnaM A Storr
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Feb 6, 2004·The Journal of Pharmacology and Experimental Therapeutics·Genya GekkerPhillip K Peterson
Jul 12, 2005·CNS Drug Reviews·Juanita Dortch-Carnes, David E Potter

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