Chemokine CCR5 receptor

FIGURE 3.12 Dependence of constitutive receptor activity as ordinates (expressed as a percent of the maximal response to a full agonist for each receptor) versus magnitude of receptor expression (expressed as the amount of human cDNA used for transient transfection, logarithmic scale) in Xenopus laevis melanophores. Data shown for human chemokine CCR5 receptors (open circles), chemokine CXCR receptors (filled triangles), neuropeptide Y type 1 receptors (filled diamonds), neuropeptide Y type 2 receptors (open squares), and neuropeptide Y type 4 receptors (open inverted triangles). Data recalculated and redrawn from [27],... 

Chao CC, Hu S, Shark KB, Sheng WS, Gekker G, Peterson PK (1997) Activation of mu opioid receptors inhibits microglial cell chemotaxis. J Pharmacol Exp Ther 281 998-1004 Chen SR, Pan HL (2006) Blocking mu opioid receptors in the spinal cord prevents the analgesic action by subsequent systemic opioids. Brain Res 1081 119-125 Chen C, Li J, Bot G, Szabo I, Rogers TJ, Liu-Chen LY (2004) Heterodimerization and crossdesensitization between the mu-opioid receptor and the chemokine CCR5 receptor. Eur J Pharmacol 483 175-186... 

Chemokine CCR5 receptor antagonists vicriviroc and mamviroc prevent viral entry into white blood cells. They are, respectively, undergoing Phase II and Phase III clinical trials for the treatment of HIV infection as part of polytherapies. ... 

Chen C, Li J, Bot G, Szabo I, Rogers TJ, Liu-Chen L-Y (2004) Heterodimerization and cross-desensitization between the X-opioid receptor and the chemokine CCR5 receptor. Eur J Pharmacol 483 175-186. 

Isik N, Hereld D, Jin T (2008) Fluorescence resonance energy transfer imaging reveals that chemokine-binding modulates heterodimers of CXCR4 and CCR5 receptors. PLoS ONE... 

Functional roles for chemokines and receptors have also been obtained through identification and analysis of polymorphisms present in a handful of these genes. As discussed previously, individuals harboring the delta-32 mutation of CCR5 are significantly resistant to HIV-1 infection. Polymorphisms in... 

Ditzel HI, Rosenkilde MM, Garred P, et al. The CCR5 receptor acts as an alloantigen in CCR5Delta32 homozygous individuals identification of chemokine and HIV-1-blocking human antibodies. Proc Natl Acad Sci U S A 1998 95 5241-5245. 

Chemokine accumulation occurs in autoimmune degenerative disease such as multiple sclerosis and in allergic inflammatory diseases such as asthma. Various viruses produce CH antagonists that interfere with the CH-mediated defence system and HIV-1 infects cells via the CCR5 receptor. 

It is unknown whether or not TMVI movements play a role in the CCR5 receptor activation mechanism. Overall, a molecular understanding of activation mechanism for CCR5 and other chemokine receptors requires further biophysical studies of transmembrane helix positions and displacements. 

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