TABLE 2.

Full opioid agonists signaling through the KOR and different Gα subunits

Concentration-response curves were generated for U50,488, salvinorin A and nalfurafine, signaling through various Gα subunits after 50-minute incubation. E_max values for U50,488 were not significantly different between Gα subunits (P = 0.53). Although EC₅₀ values varied slightly, the EC₅₀ value for U50,488 signaling through Gαz was significantly different from Gαi1, Gαi2, and GαoA (P < 0.05). E_max values for salvinorin A did not vary between Gα subunits (P > 0.98); however, salvinorin A was significantly more potent when the KOR signaled through Gαz compared with all other Gα subunits (P < 0.01). Similarly, when the KOR was coupled to Gαz, nalfurafine was more potent compared with when the KOR was coupled to any other Gα subunits (P < 0.05). Nalfurafine was similarly efficacious regardless of the Gα subunit (P > 0.05). Data are means ± S.D.; measurements were performed in duplicate in three independent experiments.

Gα	U50,488		Salvinorin A		Nalfurafine
	EC50	Emax	EC50	Emax	EC50	Emax
	nM	%	nM	%	nM	%
Gαi1	5.6 ± 1.3	99 ± 1.4	3.2 ± 0.83	99 ± 13	0.46 ± 0.0040	99 ± 1.1
Gαi2	7.9 ± 3.3	99 ± 1.1	3.1 ± 0.67	98 ± 2.1	0.38 ± 0.10	99 ± 2.1
Gαi3	2.6 ± 0.54	99 ± 1.0	2.2 ± 0.61	95 ± 5.6	0.27 ± 0.050	100 ± 7.9
GαoA	5.4 ± 0.96	99 ± 0.63	1.7 ± 0.36	100 ± 8.0	0.25 ± 0.038	99 ± 2.6
GαoB	3.5 ± 0.49	99 ± 0.31	1.6 ± 0.22	97 ± 2.8	0.37 ± 0.029	95 ± 2.9
Gαz	1.5 ± 0.85	96 ± 5.6	0.36 ± 0.048	100 ± 11	0.10 ± 0.050	110 ± 8.2