Transduction coefficients and relative activity of cannabinoid ligands at CB1 in STHdhQ7/Q7 and STHdhQ111/Q111 cells: ERK and BRET Responses
Determined using the operational model global nonlinear regression analysis (eqs. 1 and 2) in GraphPad v. 5.0. Data are expressed as mean with 95% confidence interval.
| ERK Response (Gαi/o) | BRET Response (β-arrestin1) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| logR (τ/KA) | ΔlogR (τ/KA)a | logR (τ/KA) | ΔlogR (τ/KA)a | ||||||
| WIN | STHdhQ7/Q7 | 6.35 | (6.33–6.37) | Reference ligand | 6.41 | (6.36–6.46) | Reference ligand | ||
| STHdhQ111/Q111 | 6.33 | (6.28–6.38) | Reference ligand | 6.41 | (6.38–6.44) | Reference ligand | |||
| CP | STHdhQ7/Q7 | 6.30 | (6.26–6.34) | −0.04 | (–0.09–0.01) | 6.46 | (6.41–6.52) | 0.05 | (–0.03–0.13) |
| STHdhQ111/Q111 | 6.22 | (6.17–6.27) | −0.11 | (–0.22–0.02) | 6.47 | (6.42–6.49) | 0.06 | (–0.01–0.11) | |
| 2-AG | STHdhQ7/Q7 | 6.28 | (6.20–6.36) | −0.07 | (–0.14–0.00) | 6.15 | (5.91–6.37) | −0.23 | (–0.24–0.22)*† |
| STHdhQ111/Q111 | 6.28 | (6.21–6.35) | −0.05 | (–0.11–0.01) | 6.27 | (6.36–6.38) | −0.13 | (–0.23–0.03)* | |
| AEA | STHdhQ7/Q7 | 6.35 | (6.34–6.36) | 0.00 | (–0.01–0.01) | 6.09 | (5.82–6.37) | −0.31 | (–0.33–0.29)*† |
| STHdhQ111/Q111 | 6.42 | (6.36–6.48) | 0.09 | (–0.02–0.20) | 6.22 | (6.07–6.37) | −0.18 | (–0.26–0.10)*† | |
| THC | STHdhQ7/Q7 | 4.48 | (4.43–4.54)* | −1.83 | (–2.97–0.69)* | 6.41 | (6.40–6.42)† | 0.00 | (–0.01–0.01)† |
| STHdhQ111/Q111 | 3.26 | (3.22–3.30)*^ | −3.01 | (–4.43–1.59)* | 4.98 | (4.94–5.02)*^† | −1.43 | (–1.47–1.39)*^† | |
| CBD | STHdhQ7/Q7 | N.C. | N.C. | N.C. | N.C. | ||||
| STHdhQ111/Q111 | N.C. | N.C. | N.C. | N.C. | |||||
| THC + CBD | STHdhQ7/Q7 | 2.06 | (1.91–2.21)* | −4.29 | (–5.95–2.63)* | 0.83 | (–1.91–1.95)*† | −5.58 | (–5.60–5.56)* |
| STHdhQ111/Q111 | 0.35 | (–2.01–3.69)*^ | −1.40 | (–2.77–0.33)* | 4.83 | (4.77–4.89)*^† | −1.58 | (–1.64–1.52)*^† | |
N.C., not converged.
↵* P < 0.05 compared with WIN within cell type and measurement; ^P < 0.05 compared with STHdhQ7/Q7 within ligand and measurement; †P < 0.05 compared with ERK (Gαi/o) within cell type, as determined using nonoverlapping confidence intervals (n = 4).
↵a ΔlogR (τ/KA) calculated as logR (τ/KA) test ligand – logR (τ/KA) reference ligand within cell type, where WIN is the reference ligand and ΔlogR (τ/KA) 'WIN' = 0.