Functional consequences of the TM5 mutations on the activity of H3 agonists
| Histamine pIC50 | R-α-Methylhistamine pIC50 | Imetit pIC50 | Impentamine pIC50 | |
|---|---|---|---|---|
| Wild-type | 8.63 ± 0.10 (91.6)2-a | 9.47 ± 0.18 (83.1)2-a | 9.79 ± 0.20 (83.5)2-a | 9.17 ± 0.11 (74.0)2-a |
| W196A | 9.30 ± 0.10 (89.6) | 9.99 ± 0.11 (84.5) | 9.81 ± 0.14 (84.1) | 9.35 ± 0.19 (77.2) |
| L199A | 7.45 ± 0.10 (71.9) | 7.58 ± 0.24 (50.8) | 8.94 ± 0.48 (56.9) | N.D. |
| T201A | 8.96 ± 0.05 (94.9) | 10.23 ± 0.06 (91.8) | 10.30 ± 0.01 (91.2) | 9.42 ± 0.06 (83.0) |
| A202Q | 7.39 ± 0.12 (72.0) | 8.81 ± 0.09 (77.8) | 9.11 ± 0.17 (70.4) | 9.28 ± 0.02 (62.2) |
| T204A | 9.19 ± 0.12 (93.7) | 9.92 ± 0.11 (60.0) | 10.40 ± 0.06 (62.1) | 9.39 ± 0.14 (58.4) |
| E206A | 7.29 ± 0.12 (74.1) | 6.93 ± 0.12 (74.0) | 8.56 ± 0.09 (77.5) | 8.70 ± 0.12 (78.7) |
| F208A | 7.86 ± 0.04 (88.3) | 8.84 ± 0.21 (77.8) | 9.44 ± 0.18 (70.9) | 7.74 ± 0.44 (49.3) |
HEK 293 cells expressing wild-type or mutant receptors were stimulated by agonist in the presence of 10 μM forskolin and 0.5 mM IBMX for 12 min. cAMP levels were determined, and the results shown represent the mean ± S.E. of three independent experiments performed in triplicate.
N.D., not detectable.
↵2-a Values in parentheses represent maximal percent inhibition of forskolin cAMP formation.