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  • Title: Chemokine receptor CXCR2 activates distinct pathways for chemotaxis and calcium mobilization.
    Author: Shibata F, Konishi K, Nakagawa H.
    Journal: Biol Pharm Bull; 2002 Sep; 25(9):1217-9. PubMed ID: 12230122.
    Abstract:
    Rat cytokine-induced neutrophil chemoattractant-3 (CINC-3) has neutrophil chemotactic activity comparable with that of CINC-1 and CINC-2, but induces calcium mobilization more potently than CINC-1 and CINC-2. However, only one CINC receptor, CXCR2, has been found in rat neutrophils. Therefore we attempted to determine the biochemical basis for the differences in neutrophil responses to CINC-1/-2 versus CINC-3. Both chemotactic activity and calcium mobilization induced by CINC-3 were desensitized by a 100-fold excess of CINC-1, which was consistent with our previous results showing that CINC-1 has 70-fold lower affinity to the receptor on rat neutrophils than CINC-3. Desensitization appeares to be reflected by the affinity of the ligands to the receptor. CINC-1- and CINC-3-induced chemotaxis was sensitive to inhibition by pertussis toxin, whereas calcium mobilization induced by CINC-1 and CINC-3 was insensitive. These results suggest that CINCs induce neutrophil chemotaxis and calcium mobilization through distinct G-proteins with different efficiency.
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