Potencies and efficacies of different metal ion chelator complexes on wild-type and His III:05 (His128)-CXCR3
The effect of the chemokines ITAC and IP10, the metal ion chelator complexes, the chelators, and the metal ions were measured by the phosphatidyl inositol turnover experiment in transiently transfected COS-7 cells. n refers to the number of experiments. ± values are S.E.M.
Wild-Type CXCR3 | His III:05 (His128)-CXCR3 | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Log EC50 | EC50 | n | Emax | Log EC50 | EC50 | n | Finc | Emax | Emax | |||||||||
| nM | fmol/105 cells | nM | -fold | fmol / 105 cells | % | |||||||||||||
| Endogenous chemokines | ||||||||||||||||||
| ITAC (CXCL11) | -8.8 ± 0.08 | 1.7 | 23 | 544 ± 67 | -7.8 ± 0.09 | 15 | 16 | 0.11 | 215 ± 31 | 100 | ||||||||
| IP10 (CXCL10) | -8.0 ± 0.10 | 11 | 21 | 407 ± 46 | -6.9 ± 0.22 | 163 | 14 | 0.07 | 163 ± 32 | 72 | ||||||||
| Metal ion chelator complexes | ||||||||||||||||||
| Cu(II)-Bip | -3.0 ± 0.09 | 973a | 19 | NE | -4.7 ± 0.11 | 22 | 18 | 44 | 347 ± 32 | 171 | ||||||||
| Zn(II)-Bip | -2.9 ± 0.01 | 1169a | 9 | NE | -4.3 ± 0.08 | 53 | 15 | 22 | 313 ± 33 | 153 | ||||||||
| Cu(II)-Phen | -3.5 ± 0.12 | 302a | 8 | NE | -5.1 ± 0.04 | 8.0 | 10 | 38 | 327 ± 60 | 161 | ||||||||
| Zn(II)-Phen | -3.2 ± 0.18 | 595a | 6 | NE | -4.7 ± 0.05 | 21 | 8 | 29 | 300 ± 53 | 146 | ||||||||
| Metal ions | ||||||||||||||||||
| Cu (II) | <-2 | >10,000 | 4 | NE | <-2 | >10,000 | 6 | NE | NE | |||||||||
| Zn (II) | <-2 | >10,000 | 4 | NE | <-2 | >10,000 | 6 |
| NE | NE | ||||||||
Emax, maximum stimulation; Finc, -fold increase in potency for each ligand on His III:05-CXCR3 compared with wild-type CXCR3; Emax (%), average specific efficacy of a given ligand where 100% equals the maximal specific ITAC stimulation on His III:05-CXCR3; Bip, bipyridine; Phen, phenanthrolene; NE, no detectable Emax.
↵ a The EC50 was estimated by a nonlinear regression using the sigmoidal dose-response algorithm in GraphPad Prism with a constant Hill coefficient of 1.5 corresponding to the Hill coefficient of the metal ion chelator complexes on His III:05 CXCR3.