Interactions of Opioid and Chemokine Receptors: Oligomerization of , and with CCR5 on Immune Cells

The chemokine CX3CL1/fractalkine interferes with the antinociceptive effect induced by opioid agonists in the periaqueductal grey of rats

“…Both the opioids and chemokines mediate their effects on leukocytes through the activation of GPCR. Oligomerization of mu, kappa and delta opioid receptors with the chemokine receptor CCR5 on the cell membrane of human or monkey lymphocytes has been reported and suggests that opioid receptors interact with CCR5 in cells coexpressing both receptors (Suzuki et al, 2002). The kappa opioid receptor has been shown to regulate thymocyte C-C Chemokine receptor 2 expression (Zhang and Rogers 2000) and a kappa agonist inhibits monocyte chemoattractant protein-1 (CCL2) production by human astrocytes (Sheng et al, 2003) and SDF-1alpha receptor CXCR4 expression on CD4+ lymphocytes (Lokensgard et al, 2002).…”

Heterodimerization of G Protein-Coupled Receptors: Specificity and Functional Significance

“…Conversely, coexpression of ␣ 2A AR with -OPR results in enhanced -OPR signaling in the absence of ␣ 2A AR agonist stimulation, with this effect being abolished following treatment of ␣ 2 AR agonists (Jordan et al, 2003). Finally, all three OPR subtypes have been found to interact in immune cells with the chemokine receptor CCR5 (Suzuki et al, 2002;Chen et al, 2004), with these interactions contributing to cross-desensitization between opioids and chemokines (Chen et al, 2004).…”

Naloxone acts as a potent analgesic in transgenic mouse models of sickle cell anemia

“…The synergism suggests that naloxone and morphine produce analgesia in the NY1DD mouse via different receptor systems (16). Among the numerous possibilities that could give rise to synergism are the existence of chemokine/opioid heterodimeric receptors (18,19), which may selectively recognize naloxone in Naloxone and morphine tail-flick response was measured at the time of peak analgesic activity (10, 10, and 30 min, respectively). Values for morphine apply only to NY1DD mice.…”