Effects of subtype-selective AngII receptor antagonists on agonist-induced receptor activation
| Drug Treatment | Wild-Type AT1 | AT1[AT2TM6-CT] | AT1[AT2ECL3-CT] | AT1[AT2 TM7-CT] |
|---|---|---|---|---|
| control (unstimulated) | 100 | 100 | 100 | 100 |
| AngII | 235 ± 34.63-160 | 267 ± 25.43-160 | 253 ± 14.43-160 | 202 ± 9.73-160 |
| AngII + losartan | 136 ± 23.73-164 | 260 ± 33.23-160 | 252 ± 18.33-160 | 207 ± 13.33-160 |
| AngII + PD 123319 | 218 ± 27.03-160 | 262 ± 21.03-160 | 264 ± 4.43-160 | 214 ± 11.83-160 |
| CGP 42112A | N.D. | 227 ± 13.23-160 | 211 ± 7.83-160 | 177 ± 3.13-160 |
| CGP 42112A +losartan | N.D. | 234 ± 11.13-160 | 200 ± 17.23-160 | 178 ± 7.43-160 |
| CGP 42112A + PD 123319 | N.D. | 226 ± 13.33-160 | 210 ± 3.93-160 | 168 ± 8.13-160 |
| Losartan | 106 ± 6.7 | 105 ± 3.8 | 98.7 ± 8.0 | 100 ± 4.2 |
| PD 123319 | 95.7 ± 2.3 | 106 ± 4.2 | 97.8 ± 8.0 | 96.7 ± 3.5 |
Transfected cells were treated with a submaximal concentration of either AngII (5 nM for AT1; 15 nM for AT1[AT2TM6-CT], AT1[AT2 ECL3-CT], and AT1[AT2 TM7-CT]) or CGP 42112A (100 nM for AT1[AT2 TM6-CT]; 150 nM for AT1[AT2ECL3-CT]; 250 nM for AT1[AT2 TM7-CT]) in the absence or presence of losartan (1 μM) or PD 123319 (1 μM) and release of IP3 was quantitated. Release of IP3 in drug-treated groups for each receptor is expressed as percentage of its control (unstimulated) level. The values reported represent the mean ± standard error of three to six independent experiments.