Table 3

CCK-4, peptoid, and nonpeptide efficacy at respective wild-type and mutant CCK-BRs

	Ligand efficacy
	CCK-4	PD-135,158	PD-136,450	L-740,093S
	% CCK-8-induced inositol phosphate production
Wild type	99 ± 1	20 ± 1	42 ± 2	30 ± 2^3-a
TM I
Y61A	99 ± 6	6 ± 1	16 ± 3 ^3-150	12 ± 2 ^3-150
TM II
F110A	95 ± 5	25 ± 3	47 ± 3	26 ± 4
T111A	109 ± 3	10 ± 3	16 ± 4 ^3-150	6 ± 2 ^3-150 ^3-a
TM III
S131A	103 ± 9	21 ± 2	38 ± 4	27 ± 5^3-a
G135A	103 ± 3	27 ± 7	46 ± 10	24 ± 2
TM IV
M186A	92 ± 8	41 ± 8 ^3-150	67 ± 7 ^3-150	9 ± 2 ^3-150
T193A	95 ± 5	29 ± 3	44 ± 3	25 ± 2
TM V
S219A	106 ± 10	19 ± 3	43 ± 2	42 ± 6^3-a
L226A	100 ± 3	26 ± 3	48 ± 2	25 ± 1
F227A	104 ± 6	0 ± 0 ^3-150	8 ± 3 ^3-150	41 ± 4
TM VI
W346A	99 ± 5	43 ± 5 ^3-150	57 ± 3	12 ± 3 ^3-150 ^3-a
V349A	103 ± 5	3 ± 2 ^3-150	3 ± 3 ^3-150	72 ± 8 ^3-150 ^3-a
Y350A	98 ± 3	0 ± 2 ^3-150	0 ± 2 ^3-150	0 ± 3 ^3-150 ^3-a
N353L	85 ± 4	9 ± 2	15 ± 2 ^3-150	12 ± 1 ^3-150 ^3-a
T354A	96 ± 8	34 ± 5	53 ± 7	5 ± 2 ^3-150
TM VII
S379A	101 ± 2	31 ± 5	51 ± 1	44 ± 6^3-a

Multiple CCK-BR pocket mutations significantly alter efficacy of the synthetic peptoid (PD-135,158, PD-136,450) and nonpeptide (L-740,093S) ligands (values are underlined). Mutant CCK-BRs were stimulated with saturating ligand concentrations which were at least 50-fold higher than their respective IC₅₀ values (Table1). IC₅₀ values for L-740,093S at the mutant receptors (not shown) were not significantly different from the wild-type value (25 ± 3.7 nM) except for the T111A (84 ± 10.9 nM) and S379A mutants (8.8 ± 1.6 nM). Data represent means ± S.E. of at least three independent experiments.

TM, transmembrane domain.
↵3-a Previously reported data (Bläker et al., 1998).
↵3-150 P < 0.05 versus wild type.