Table 1. Ins(1,4,5)P₃R Binding and Ca²⁺ Release Mediated by Ins(1,4,5)P₃, AdA, and Compounds 2–7^a.

	Ca2+ release			binding
ligand	pEC50; EC50	release (%)	h	pKd; Kd (nM)	h	EC50/Kd	EC39/Kdb
Ins(1,4,5)P3	6.90 ± 0.12; 126 nM	78.8 ± 1.3	0.7 ± 0.1	8.06 ± 0.03; 8.7	1.1 ± 0.2	14 (5–46)	17 (5–63)
2	4.06 ± 0.09c; 87.7 μM	56.2 ± 2.6c	1.4 ± 0.2	5.91 ± 0.03c; 1230	0.9 ± 0.1	71 (34–148)	132 (49–355)
3	3.98 ± 0.04c; 104 μM	53.1 ± 5.0c	1.3 ± 0.2	6.26 ± 0.07c; 549	0.9 ± 0.1	191c (123–295)	462c (128–1667)
4	ND	4.3 ± 2.1d	ND	48 ± 12e	ND	ND
5	ND	5.9 ± 2.1d	ND	53 ± 3e	ND	ND
6	5.53 ± 0.20c; 2.96 μM	78.8 ± 3.0	0.9 ± 0.2	6.89 ± 0.09c; 129	0.7 ± 0.1	23 (5–105)
7	7.09 ± 0.18; 80 nM	75.2 ± 1.4	1.0 ± 0.1	7.95 ± 0.05; 11.2	1.1 ± 0.2	7 (2–29)
AdA	7.62 ± 0.12c; 24 nM	77.8 ± 4.5	0.8 ± 0.1	8.86 ± 0.14c; 1.4	1.2 ± 0.2	17 (5–51)

^aEffects of ligands on Ca²⁺ release from the intracellular stores of permeabilized HEK-Ins(1,4,5)P₃R1 cells and on [³H]-Ins(1,4,5)P₃ binding to cerebellar membranes are summarized. Results from functional assays are means ± SEM (pEC₅₀ (−log of the half-maximally effective concentration), Ca²⁺ release (%), and Hill coefficient (h)) and means (EC₅₀) from 5 to 11 independent experiments, each performed in duplicate. Results from binding experiments are means ± SEM (pK_d (−log of the equilibrium dissociation constant) and h) and means (K_d) from three independent experiments. The pK_d values for Ins(1,4,5)P₃ and AdA have been published (Mills et al.)⁴³ and are reproduced with permission. Final columns show EC₅₀/K_d or (for partial agonists and Ins(1,4,5)P₃) EC₃₉/K_d (mean and 95% CI). ND, not determined.

^bEC₃₉ reports the concentration of ligand required to evoke the same Ca²⁺ release (39% of the intracellular stores) as evoked by a half-maximally effective concentration of Ins(1,4,5)P₃.

^cP < 0.05 relative to Ins(1,4,5)P₃.

^dCa²⁺ release evoked by 300 μM ligand.

^eSpecific binding of [³H]-Ins(1,4,5)P₃ in the presence of 30 μM competing ligand.