Pharmacological characterization of the chemokine receptor, CCR5

Br J Pharmacol. 2002 Feb;135(4):1033-43. doi: 10.1038/sj.bjp.0704540.

Abstract

1. We investigated the effects of a number of naturally occurring chemokines (MIP-1alpha, MIP-1beta, 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. 2. Internalization of CCR5 following chemokine treatment was studied and MIP-1alpha, MIP-1beta and RANTES (50 nM) were able to induce internalization (similar50%) of the receptor. Internalization due to MCP-2, MCP-3 and MCP-4 was less (similar20%). 3. Phosphorylation of CCR5 following chemokine treatment was studied and MIP-1alpha, MIP-1beta and RANTES (50 nM) were able to induce phosphorylation of CCR5 whereas the other chemokines did not induce CCR5 phosphorylation. 4. MIP-1alpha, MIP-1beta, RANTES and MCP-2 were able to stimulate [(35)S]-GTPgammaS 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 (similar80%) compared to MIP-1alpha, MIP-1beta and RANTES, which gave similar maximal stimulations in this assay. 5. MIP-1alpha, MIP-1beta, 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. 6. It is concluded that different chemokines interacting with CCR5 mediate different patterns of cellular responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Calcium / metabolism
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / pharmacology
  • Chemokines / pharmacology*
  • Cricetinae
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Intracellular Fluid / metabolism
  • Macrophage Inflammatory Proteins / pharmacology
  • Monocyte Chemoattractant Proteins / pharmacology
  • Phosphorylation
  • Precipitin Tests
  • Receptors, CCR5 / drug effects*
  • Receptors, CCR5 / metabolism

Substances

  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines
  • Macrophage Inflammatory Proteins
  • Monocyte Chemoattractant Proteins
  • Receptors, CCR5
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Calcium