TABLE 4
Pharmacological analysis of mutant human H4R proteins, using [3H]histamine saturation analysis and displacement studies Equilibrium Kd and Bmax values for [3H]histamine (picomole per milligram protein) and pKi of ligands for the indicated H4R mutants are presented as average ± S.E.M. of results of at least three independent experiments. The figure in the panel shows the human H4R amino acid sequence that was replaced by the mouse H4R sequence as in chimera 10. The residues that are identical to those of the mouse H4R are indicated in white, whereas the ones that differ are shown in black. The amino acid residues of the human H4R indicated in this table are altered into the corresponding residues of the mouse H4R.
 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Receptor | Kd | Bmax | pKi | |||||||
| Histamine | Clozapine | VUF 8430 | ||||||||
| nM | ||||||||||
| hH4R | 9.0 ± 0.1 | 2.71 ± 1.00 | 7.89 ± 0.05 | 6.35 ± 0.03 | 7.46 ± 0.02 | |||||
| mH4R | 77.5 ± 11 | 1.48 ± 0.24 | 7.09 ± 0.04 | 5.49 ± 0.07 | 6.75 ± 0.10 | |||||
| V141I | 10.5 ± 1.4 | 2.00 ± 0.39 | 7.66 ± 0.08 | 6.19 ± 0.05 | 7.59 ± 0.05 | |||||
| V153A | 12.9 ± 3.2 | 1.04 ± 0.11 | 7.72 ± 0.14 | 6.23 ± 0.05 | 7.46 ± 0.09 | |||||
| E155D | 11.1 ± 3.4 | 1.97 ± 0.24 | 7.61 ± 0.04 | 6.23 ± 0.02 | 7.41 ± 0.06 | |||||
| DEGSE→ NSTNTKD | 10.2 ± 2.1 | 1.52 ± 0.31 | 7.65 ± 0.07 | 6.44 ± 0.04 | 7.52 ± 0.05 | |||||
| F169V | 42.4 ± 9.7 | 1.88 ± 0.34 | 7.12 ± 0.10 | 5.52 ± 0.05 | 7.05 ± 0.05 | |||||
| S170T | 11.9 ± 2.0 | 1.13 ± 0.23 | 7.82 ± 0.06 | 6.02 ± 0.03 | 7.60 ± 0.05 | |||||
| A176T | 8.5 ± 1.3 | 1.54 ± 0.33 | 7.76 ± 0.05 | 6.18 ± 0.03 | 7.52 ± 0.06 | |||||
| S179M | 18.0 ± 1.3 | 2.73 ± 0.58 | 7.57 ± 0.06 | 6.27 ± 0.05 | 7.52 ± 0.06 | |||||
| F180L | 7.8 ± 1.0 | 3.10 ± 0.38 | 8.06 ± 0.07 | 6.37 ± 0.04 | 7.65 ± 0.09 | |||||