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PMID: 11861332 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Pharmacological characterization of the chemokine receptor, CCR5.

British journal of pharmacology ·Vol. 135 ·No. 4 ·2002-02-00 ·Pages 1033-43

Mueller A, Mahmoud NG, Goedecke MC, McKeating JA, Strange PG

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.

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,metabolism
Chemicals
Chemokine CCL3 Chemokine CCL4 Chemokine CCL5 Chemokines Macrophage Inflammatory Proteins Monocyte Chemoattractant Proteins Receptors, CCR5 Guanosine 5'-O-(3-Thiotriphosphate) Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mueller Anja
School of Animal and Microbial Sciences, The University of Reading, PO Box 228, Reading RG6 6AJ.
Mahmoud Nasir G
Goedecke Marc C
McKeating Jane A
Strange Philip G
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0704540
Published
2002-02-00
Pages
1033-43
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1573204
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjp.0704540 PMC Full Text View journal details
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