19
Views
0
CrossRef citations to date
0
Altmetric
Papers

Modulation of neuronal CXCR4 by the μ-opioid agonist DAMGO

, , , , &
Pages 492-500 | Received 14 Jun 2006, Accepted 21 Sep 2006, Published online: 10 Jul 2009
 

Abstract

The chemokine receptor CXCR4 regulates neuronal survival and differentiation and is involved in a number of pathologies, including cancer and human immunodeficiency virus (HIV). Recent data suggest that chemokines act in concert with neurotransmitters and neuropeptides, such as opioids. This study aimed to determine whether μ-opioid agonists alter the effect of CXCL12 (the specific CXCR4 ligand) on central neurons. Neuronal expression of CXCR4 and μ-opioid receptors (MORs) was analyzed by Western blot, immunostaining, and flow cytometry. Single-cell studies showed that all CXCR4-positive neurons coexpress MORs. Treatment of neuronal cultures with the selective MOR agonist DAMGO or the endogenous peptide endomorphin-1 inhibited intracellular signaling pathways (ERK1/2 and Akt) activated by CXCL12. Furthermore, DAMGO abolished the neuroprotective effect of CXCL12 in N-methyl-d-aspartate (NMDA) neurotoxicity studies. The effects of DAMGO and endomorphin-1 were inhibited by a general or a μ-specific opioid receptor antagonist, and not caused by changes in neuronal CXCR4 levels. DAMGO did not affect CXCL12-induced internalization of CXCR4. The authors propose that interactions between MOR and CXCR4 signaling can modulate the action of CXCL12 on neuronal survival—which may have important implications to neuroAIDS as well as other neuroinflammatory disorders.

The authors thank Alessandro Fatatis and Robert Nichols for discussion and critical reading of the manuscript, Randi Hippensteel for technical assistance with the cultures, and NIH-NIDA for support (grants DA-15014 and DA-19808 to O.M.; NRSA fellowship DA-020234 to JP).

Log in via your institution

Log in to Taylor & Francis Online

There are no offers available at the current time.

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.