Chemokine desensitization

In this chapter, we review the interactions at the level of protein function, between opioid receptors and chemokine receptors, using both in vitro and in vivo model systems. As a part of this discussion, we also describe our current understanding of the biochemical pathway(s) that are involved in the heterologous desensitization process between these groups of receptors. 

Certain Chemokine Receptors Cross-Desensitize Opioid Receptors... 

Opioid Receptors Cross-Desensitize Chemokine Receptors... 

Giimm MC, Ben-Baruch A, Taub DD, Howard OM, Resau JH, Wang JM (1998) Opiates transde-activate chemokine receptors delta and mu opiate receptor-mediated heterologous desensitization. J Exp Med 188(2) 317-325... 

There is a definite trend of bidirectional cross-talk between opioid and chemokine receptors in the central nervous system. In vitro, as well as in vivo studies, have shown desensitization of CXCR4 by MOR and thus prevent the neuroprotective action of this chemokine. Although the precise molecular mechanism underlying this cross-talk is still under investigation, based on the evidences in literature several possible pathways can be expected to act independently or in concert and lead to the deficit of CXCR4 function. Our studies have shown that p opioids can increase the brain levels of FHC which can subsequently block CXCR4 signaling. Eurther studies... 

Zhang N, Rogers TJ, Caterina M, Oppenheim JJ (2004) Proinflammatory chemokines, such as C-C chemokine hgand 3, desensitize mu-opioid receptors on dorsal root ganglia neurons. J Immunol 173 594-599... 

KohoutTA, Nicholas SL, Perry SJ, Reinhart G, Junger S, Struthers RS. Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7. J Biol Chem 2004 279(22) 23214-23222. 

Mariani M, Lang R, Binda E, Panina-Bordignon P, D Ambrosio D. Dominance of CCL22 over CCL17 in induction of chemokine receptor CCR4 desensitization and internalization on human Th2 cells. Eur J Immunol 2004 34(1) ... 

Aramori I, Ferguson SS, Bieniasz PD, Zhang J, Cullen B, Cullen MG. Molecular mechanism of desensitization of the chemokine receptor CCR-5 receptor signaling... 

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