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GTPγS Incorporation in the Rat Brain: A Study on μ-Opioid Receptors and CXCR4
Journal article   Open access   Peer reviewed

GTPγS Incorporation in the Rat Brain: A Study on μ-Opioid Receptors and CXCR4

Silvia Burbassi, Vincent Aloyo, Kenny Simansky and Olimpia Meucci
Journal of neuroimmune pharmacology, v 3(1), pp 26-34
Mar 2008
PMID: 18247130
url
https://doi.org/10.1007/s11481-007-9083-1View
Published, Version of Record (VoR) Open

Abstract

Neurosciences chemokine Biomedicine Immunology CXCL12 DAMGO GPCR CNS Pharmacology/Toxicology Cell Biology Virology morphine
Chemokine and opioid receptors are G-protein-coupled receptors that play important roles in both the central nervous system and the immune system. The long-term goal of our research is to establish whether opioids regulate the activity of the chemokine receptor CXCR4 (one of the major HIV co-receptors) in the brain. In this research, we studied the anatomical distribution of functional receptors in young and adult animals by using the [35S]GTPγS “binding” assay as an indication of G-protein activation by CXCL12 (the natural CXCR4 ligand) or by μ-opioid agonists. Brain slices or homogenates from Holtzmann rats of different ages (from 2 to 21 days old and adult animals) were treated with CXCL12 (0.001–100 nM), d-ala2,MePhe4,gly-ol5]enkephalin (DAMGO; 0.0003–10 μM) or morphine (0.0003–10 μM) and then processed for the assay. Our results show stimulation of both μ-OR and CXCR4 in several brain areas, including cortex and hippocampus (p < 0.001); this effect is dose and age dependent, and the magnitude of response varies among different brain regions. Furthermore, AMD3100 (100 ng/ml), a specific CXCR4 antagonist, abolished CXCL12 stimulation in all the brain regions analyzed (p < 0.001). Our findings suggest a similar pattern of expression for μ-OR and CXCR4 in the brain, supporting the possibility of an interaction between the two G-protein-coupled receptors in vivo. This might be relevant to the role of opiates in HIV neuropathogenesis.

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