Opioids desensitization

Bohn LM, Gainetdinov RR, Lin FT et al (2000) p-Opioid receptor desensitization by (3-arrestin-2 determines morphine tolerance but not dependence. Nature 408 720-723... 

Receptor desensitization, internalization, and/or down-regulation may play a role in the development of tolerance to opioid receptor agonists (Clark et al. 

Bleich A, Gelkopf M, Weizman T, et al Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel characteristics and a pharmacotherapeutic approach. Isr J Psychiatry Relat Sci 39 104-112, 2002 Bohn LM, Gainetdinov RR, Lin FT, et al Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 408 720— 723, 2000... 

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... 

Bohn LM, Dykstra LA, Lefkowitz RJ, Caron MG, Barak LS (2004) Relative opioid efficacy is determined by the complements of the G protein-coupled receptor desensitization machinery. Mol Pharmacol 66 106-112... 

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... 

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