Pharmacological characterization of the chemokine receptor, CCR5
Mueller A., Mahmoud NG., Goedecke MC., McKeating JA., Strange PG.
We investigated the effects of a number of naturally occurring chemokines (MIP‐1α, MIP‐1β, RANTES, MCP‐2, MCP‐3, MCP‐4) on different processes linked to the chemokine receptor CCR5 in recombinant CHO cells expressing the receptor at different levels. Internalization of CCR5 following chemokine treatment was studied and MIP‐1α, MIP‐1β and RANTES (50 nM) were able to induce internalization (∼50%) of the receptor. Internalization due to MCP‐2, MCP‐3 and MCP‐4 was less (∼20%). Phosphorylation of CCR5 following chemokine treatment was studied and MIP‐1α, MIP‐1β and RANTES (50 nM) were able to induce phosphorylation of CCR5 whereas the other chemokines did not induce CCR5 phosphorylation. MIP‐1α, MIP‐1β, RANTES and MCP‐2 were able to stimulate [35S]‐GTPγS binding, an index of receptor/G protein activation, whereas MCP‐3 and MCP‐4 had no effect in this assay. MCP‐2 was a partial agonist (∼80%) compared to MIP‐1α, MIP‐1β and RANTES, which gave similar maximal stimulations in this assay. MIP‐1α, MIP‐1β, RANTES, MCP‐2 and MCP‐4 were able to stimulate increases in intracellular calcium ions via activation of CCR5 whereas MCP‐3 was without effect. It is concluded that different chemokines interacting with CCR5 mediate different patterns of cellular responses. British Journal of Pharmacology (2001) 135, 1033–1043; doi:10.1038/sj.bjp.0704540