Table 1.

Impact of bile acids on ligand binding and biological activity

	Binding		Biological Activity
	pIC50	Specific binding, %control	pEC50	Emax, %
	Effects on CCK on wild-type CCK receptors expressed in normal membrane or elevated cholesterol
CCK1R
Control	8.62 ± 0.11	100	10.94 ± 0.07	70 ± 4
TCDC, 0.5 mM	7.90 ± 0.08**	50 ± 4**	10.14 ± 0.13**	60 ± 6
TUDC, 1 mM	8.67 ± 0.10	101 ± 5	10.92 ± 0.17	80 ± 3
CCK2R
Control	9.12 ± 0.10	100	9.54 ± 0.06	53 ± 5
TCDC, 0.5 mM	9.55 ± 0.28	85 ± 11	9.42 ± 0.07	43 ± 3
TUDC, 1 mM	8.70 ± 0.13	106 ± 3	9.40 ± 0.11	64 ± 6
SRD15-CCK1R
Control	9.12 ± 0.19	100	9.59 ± 0.16	92 ± 4
TCDC, 0.5 mM	9.15 ± 0.23	104 ± 1	9.60 ± 0.35	70 ± 4**
TUDC, 0.1 mM			10.69 ± 0.19**	82 ± 8
TUDC, 1 mM	8.77 ± 0.08	97 ± 5	10.99 ± 0.18**	79 ± 6
	Effects on allosteric ligand binding and action on wild-type CCK1R in normal membrane
BDZ-1
Control	8.82 ± 0.14	100
TCDC, 0.5 mM	9.03 ± 0.21	55 ± 5**
TUDC, 1 mM	8.67 ± 0.06	96 ± 4
T-0632
Control	9.43 ± 0.02	100
TCDC, 0.5 mM	9.60 ± 0.06	66 ± 6**
TUDC, 1 mM	9.50 ± 0.02	100 ± 5
GI181771X
Control			9.43 ± 0.12	47 ± 5
TCDC, 0.5 mM			8.29 ± 0.10**	31 ± 3*
TUDC, 1 mM			9.27 ± 0.29	41 ± 3
	Effects on CCK binding and action on mutant CCK1R constructs in normal membrane
CCK1R-Y140A
Control	9.68 ± 0.26	100	9.08 ± 0.08	71 ± 3
TCDC, 0.5 mM	9.78 ± 0.48	63 ± 7	8.88 ± 0.10	55 ± 9*
TUDC, 1 mM	9.40 ± 0.05	104 ± 5	8.99 ± 0.16	64 ± 7
CCK1R-Y237A
Control	7.78 ± 0.14	100	10.64 ± 0.20	79 ± 3
TCDC, 0.5 mM	7.06 ± 0.17*	55 ± 6	9.45 ± 0.28**	79 ± 9
TUDC, 1 mM
CCK1R-W166A
Control	NDB	NDB	9.01 ± 0.10	58 ± 6
TCDC, 0.5 mM	NDB	NDB	>8.0**	33 ± 2**
TUDC, 1 mM	NDB	NDB

Values are means ± SE. ¹²⁵I-BDZ-1 and ¹²⁵I-T-0632 were utilized for binding BDZ-1 and T-0632, respectively; for all other binding, ¹²⁵I-CCK radioligand was used.

CCK1R, CCK type 1 receptor; E_max, maximal response to 0.1 mM ATP; TCDC, taurochenodeoxycholic acid; TUDC, tauroursodeoxycholic acid.

^*P < 0.05,

^**P < 0.01 vs. control.

NDB, no detectable binding.