CXCR4 receptor desensitization

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... 

I., Sozzani, S., Peiper, S.C., Horuk, R., Ali, H., and Snyderman, R. (1997) Regulation of human chemokine receptors CXCR4. Role of phosphorylation in desensitization and internalization. The Journal of Biological Chemistry, 272, 28726-28731. 

McCormick, P.J., Segarra, M., Gasperini, P., Gulino, A.V., and Tosato, G. (2009) Impaired Recruitment of Grk6 and beta-Arrestin . Causes Delayed Internalization and Desensitization of a WHIM Syndrome-Associated CXCR4 Mutant Receptor. PLoS One, 4, e8102. 

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