Table 2. Relative potencies of IP3 analogues at different IP3 receptor subtypes.
IP3R1 | IP3R2 | IP3R3 | |||||||
ΔpEC50 | Δmax (%) | (1,4,5)IP3max (%) | ΔpEC50 | Δmax (%) | (1,4,5)IP3max (%) | ΔpEC50 | Δmax (%) | (1,4,5)IP3max (%) | |
(4,5)IP2 | 1.92±0.15 | 13±5 | 81±3 | 1.92±0.05 | 8±3 | 65±4 | 1.38±0.06* | −1±2 | 77±4 |
2-deoxy(1,4,5)IP3 | 0.09±0.10 | −1±2 | 81±3 | 0.19±0.14 | −3±3 | 63±4 | −0.17±0.08 | 0±2 | 77±4 |
(1,4,6)IP3 | 1.57±0.09 | −2±5 | 76±5 | 1.67±0.15 | −3±6 | 64±5 | 1.45±0.09 | 8±6 | 55±7 |
3-deoxy(1,4,5)IP3 | 1.61±0.12 | 21±2* | 80±4 | 1.64±0.21 | 12±4* | 68±3 | 1.66±0.17 | 20±5* | 66±3 |
(1,3,4,5)IP4 a | 2.09±0.07 | 17±5a | 77±1 | 2.18±0.04 | 7±0* | 67±6 | 2.38±0.07 | NDa | 77±4 |
MG(1,4,5)IP3 | 0.69±0.10 | 4±5 | 77±3 | 0.7±0.14 | 11±3* | 64±3 | 0.64±0.15 | 4±4 | 61±3 |
From paired comparisons with (1,4,5)IP3, the relative potency and differences in maximal Ca2+ release
are shown for each analogue at each IP3R subtype. Results show means ± SEM, with n provided in Table 1. To allow direct comparison with responses evoked by (1,4,5)IP3, maximal Ca2+ release evoked by (1,4,5)IP3 in experiments paired with the analogues are also shown ((1,4,5)IP3 max).
With (1,3,4,5)IP4 it was impossible to attain concentrations (>100 µM) that evoked a maximal response for all IP3R subtypes; in these cases the maximal responses were not subject to statistical analysis. The relative potency of (1,3,4,5)IP4 at IP3R subtypes was estimated by assuming it was a full agonist that released the same fraction of the intracellular Ca2+ stores as a maximally effective concentration of (1,4,5)IP3 in parallel analyses. ND, not determined.
Denotes values significantly different (P<0.05) from IP3R1 (for ΔpEC50 values) or from (1,4,5)IP3 in paired comparisons with the analogue (for Δmax values).