TABLE 1.

Potency and efficacy of dynorphin peptides signaling through the KOR and different Gα subunits

Concentration-response curves were generated for the dynorphin peptides signaling through the KOR and various Gα subunits after 50-minute incubation. Although the E_max values for dynorphin A (1–17) were not significantly different regardless of the Gα subunit (P > 0.5), dynorphin A (1–17) had a statistically significant lower EC₅₀ value when the KOR was signaling through Gαz compared with the other Gα subunits (P ≤ 0.05). Dynorphin A (1–13) was significantly more potent when the KOR signaled through Gαz compared with Gαi3 (P = 0.011). In addition, dynorphin A (1–13) was more efficacious through Gαz compared with either GαoA (P < 0.001) or GαoB (P < 0.05). Similarly, dynorphin B (1–13) was more potent when the KOR signaled through Gαz compared with Gαi1 (P < 0.01). Dynorphin B (1–13) was more efficacious through Gαz compared than GαoA (P = 0.01). Although α-neo-endorphin had a similar efficacy regardless of Gα subunit (P > 0.26), it was significantly more potent when the KOR signaled through Gαz compared with all other Gα subunits (P < 0.05). All values are means ± S.D.; measurements were performed in duplicate in three independent experiments.

Gα	Dynorphin A (1–17)		Dynorphin A (1–13)		Dynorphin B (1–13)		α-Neo-Endorphin
	EC50	Emax	EC50	Emax	EC50	Emax	EC50	Emax
	nM	%	nM	%	nM	%	nM	%
Gαi1	23 ± 4.4	97 ± 5.0	5.8 ± 1.7	95 ± 7.0	28 ± 14	97 ± 3.1	54 ± 9.8	100 ± 5.2
Gαi2	52 ± 11	98 ± 3.1	6.1 ± 0.45	97 ± 1.4	6.2 ± 0.50	94 ± 4.2	110 ± 40	98 ± 13
Gαi3	45 ± 0.93	99 ± 0.97	12 ± 7.1	96 ± 6.6	13 ± 5.5	100 ± 7.5	26 ± 9.4	100 ± 6.0
GαoA	30 ± 8.5	91 ± 5.5	5.8 ± 0.17	70 ± 6.6	5.7 ± 1.8	88 ± 2.7	45 ± 2.3	88 ± 5.5
GαoB	43 ± 7.7	97 ± 11	5.9 ± 2.7	84 ± 6.5	11 ± 2.3	92 ± 1.4	78 ± 9.5	91 ± 8.8
Gαz	9.6 ± 2.7	97 ± 6.8	0.85 ± 0.20	96 ± 3.3	3.7 ± 2.3	96 ± 6.1	6.0 ± 1.5	96 ± 4.5