Differential effects of the F340L mutation on the ability of agonists to activate PI hydrolysis
| Drug | Native ReceptorKact | Native ReceptorVmax | F340L MutantKact | F340L Mutant Vmax |
|---|---|---|---|---|
| nM | % | μM | % | |
| (−)-DOB | 59 ± 15 | 100 ± 3.4 | 32 ± 16 | 50 ± 19 |
| (±)-DOI | 11.6 ± 3 | 93 ± 3 | 26 ± 12 | 100 |
| DOM | 171 ± 32 | 93 ± 4 | 28 ± 14 | 50 ± 4 |
| Bufotenine | 127 ± 24 | 90 ± 14 | 1.9 ± 1.9 | 10.5 ± 1.4 |
| DMT | 731 ± 239 | 77 ± 5 | ND2-a | <10 |
| 5-OMe-DMT | 988 ± 169 | 86 ± 2.6 | ND | <10 |
| α-Methyltryptamine | 1331 ± 529 | 99 ± 12 | ND | <10 |
| 5-HT | 62 ± 20 | 100 | 7.2 ± 2 | 18 ± 3 |
| α-Methyl-5-HT | 65 ± 9.3 | 100 | 6.3 ± 2 | 65 ± 13 |
| Quipazine | 395 ± 36 | 100 | ND | 0 |
↵2-a ND, not detectable (<20% increase of PI hydrolysis over basal). For a typical experiment with stably transfected cells expressing the 5-HT2A receptor, the basal activity was 2,000 dpm, with the maximum stimulation with saturating concentrations of (−)-DOB being 46,180 dpm (23-fold stimulation). For the M1C15 cell line, the basal level was 600 dpm, with the maximum stimulation with saturating concentrations of (±)-DOI being 27,250 dpm (45-fold stimulation). V max is expressed as the percentage of maximum stimulation of 5-HT.