ABCMdb

ABCC1 p.Lys332Leu

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PMID: 12186871 [PubMed] Haimeur A et al: "Charged amino acids in the sixth transmembrane helix of multidrug resistance protein 1 (MRP1/ABCC1) are critical determinants of transport activity."

No. Sentence Comment

47 The sequences of the individual sense strands, with the altered codons underlined and the corresponding changes in amino acids indicated in parentheses were as follows: (K332D) 5Ј-CTC ATG AGC TTC TTC TTC GAC GCC ATC CAC GAC CTG-3Ј; (K332L) 5Ј-CTC ATG AGC TTC TTC TTC CTG GCC ATC CAC GAC CTG-3Ј; (H335E) 5Ј-GC TTC TTC TTC AAG GCC ATC GAG GAC CTG ATG ATG-3Ј; (H335L) 5Ј-GC TTC TTC TTC AAG GCC ATC TTG GAC CTG ATG ATG-3Ј; (H335Q) 5Ј-GC TTC TTC TTC AAG GCC ATC CAG GAC CTG ATG ATG-3Ј; (D336R) 5Ј-C AAG GCC ATC CAC CGG CTG ATG ATG TTT TCG-3Ј; (D336L) 5Ј-C AAG GCC ATC CAC CTG CTG ATG ATG TTT TCG-3Ј. Login to comment
106 In the case of the MRP1-Lys332 mutants K332D and K332L (Fig. 3B) and the MRP1-Asp336 mutants D336L and D336R (Fig. 3D), LTC4 uptake was reduced to levels that were indistinguishable from those observed with vesicles prepared from empty vector-transfected control cells. Login to comment
131 In contrast, LTC4 had very little effect (Ͻ15%) on E217betaG uptake by MRP1 mutants K332D and K332L, indicating that loss of LTC4 transport in these mutants is associated with a loss of binding of this substrate. On the other hand, LTC4 was still able to inhibit E217betaG uptake by MRP1 mutants H335E, H335L, and H335Q, which is consistent with only a partial reduction in LTC4 transport activity observed with these mutants (Fig. 6B). Login to comment
140 B, wild-type MRP1 (f), MRP1 mutants K332D (Œ) and K332L (‚), and control empty pcDNA3.1(-) vector (E). Login to comment
152 However, this band is not detectable in [3 H]LTC4 photolabeled proteins from cells expressing comparable levels of the MRP1 mutants K332D and K332L or mutants D336L and D336R, indicating that these mutations abrogate photolabeling and hence binding of this compound. Login to comment
160 The relative levels of [3 H]GSH uptake by the MRP1 K332D and K332L mutants were less than 15% of wild-type MRP1 (Fig. 7A) after subtracting basal [3 H]GSH transport by membrane vesicles from the empty vector-transfected control cells. Login to comment
163 Membrane vesicles prepared from transfected cells were incubated at 37 °C with 400 nM [3 H]E217betaG in transport buffer for the times indicated. A, time courses of ATP-dependent [3 H]E217betaG uptake by membrane vesicles prepared from HEK293T cells transfected with wild-type MRP1 (f), TM6 mutants K332D (Œ) and K332L (‚), and the empty pcDNA3.1(-) vector (E). Login to comment
170 A, ATP-dependent [3 H]E217betaG uptake in membrane vesicles from cells expressing wild-type MRP1 (WT-MRP1) (open bars), TM6 mutants K332D and K332L (shaded bars), and the empty pcDNA3.1(-) vector control (solid bars). Login to comment
183 Substitution of Lys332 with a neutral (K332L) or negatively charged (K332D) amino acid had no effect on MTX uptake by MRP1. Login to comment
190 Thus, replacing Lys332 with either Leu or Asp eliminated the ability of MRP1 to transport LTC4 (and markedly reduced GSH transport) without affecting the transport of other organic anions including E217betaG, estrone 3-sulfate, and MTX. Login to comment
204 Membrane vesicles were preincubated with acivicin and then incubated with [3 H]GSH in the presence of 30 ␮M apigenin in transport buffer for 20 min at 37 °C. A, K332D and K332L; B, H335E, H335L, and H335Q; C, D336L and D336R. Login to comment
206 D, WT-MRP1 (f); K332D (Œ); K332L (‚); vector control (E). Login to comment

PMID: 15155831 [PubMed] Haimeur A et al: "Mutations of charged amino acids in or near the transmembrane helices of the second membrane spanning domain differentially affect the substrate specificity and transport activity of the multidrug resistance protein MRP1 (ABCC1)."

No. Sentence Comment

100 We showed previously that nonconservative substitutions of Lys332 with either Asp (K332D) or Leu (K332L) led to a selective loss of transport of GSH and the GSH conjugate, LTC4 (Haimeur et al., 2002). Login to comment
121 The same-charge mutant K332R, like the K332D and K332L mutants described previously (Haimeur et al., 2002), exhibited transport levels of the conjugated estrogens E217betaG and E13SO4 and the antifolate MTX that were comparable with wild-type MRP1 (Table 2); however, GSH transport by K332R was very low compared with wild-type MRP1 and similar to that which we reported previously for the K332D/L mutants (Fig. 3B). Login to comment

PMID: 15161912 [PubMed] Leslie EM et al: "Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Evidence that a tri-glutathione conjugate is required."

No. Sentence Comment

69 MRP1 and MRP2 Expression Vectors and Transfections in HEK293T Cells-The construction and expression of wild-type MRP1 (WT-MRP1), wild-type MRP2 (WT-MRP2), and the MRP1 mutants K332L, D336K, K319D, and K347D in HEK293T cells have been described previously (31, 35-37). Login to comment
204 To determine whether these amino acid residues are critical for transport of As(GS)3, transport assays were done using membrane vesicles prepared from HEK293T cells transfected with pcDNA3.1(-) (empty vector), WT-MRP1, D336K-MRP1, K332L-MRP1, K319D-MRP1, and K347D-MRP1 cDNAs. Login to comment
206 Consistent with the selective loss of LTC4 and GSH transport by K332L-MRP1 and the general loss of transport function by D336K-MRP1, these mutants also did not transport As(GS)3 (Fig. 8B). Login to comment
222 As(GS)3 transport by wild-type and mutant K332L, D336K, K319D, K347D-MRP1. Login to comment
223 A, membrane vesicles prepared from HEK293T cells transfected with empty vector (pcDNA3.1(-)), wild-type MRP1 (WT-MRP1), or mutant MRP1 (K332L-MRP1, D336K-MRP1, K319D-MRP1, or K347D-MRP1) were immunoblotted with the MRP1-specific mAb QCRL-1 as described under "Experimental Procedures." Login to comment

PMID: 17295059 [PubMed] Chang XB et al: "A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1."

No. Sentence Comment

109 P343A, K332L and K332D mutations in TM6 resulted in significantly reduced transport of some organic anion substrates [75, 76]. Login to comment

PMID: 18775981 [PubMed] Grant CE et al: "Structural determinants of substrate specificity differences between human multidrug resistance protein (MRP) 1 (ABCC1) and MRP3 (ABCC3)."

No. Sentence Comment

305 In addition, photolabeling with [3 H]LTC4 of K332D and K332L mutant proteins was severely reduced compared with wild-type MRP1. Login to comment

PMID: 19398503 [PubMed] Maeno K et al: "Molecular basis for reduced estrone sulfate transport and altered modulator sensitivity of transmembrane helix (TM) 6 and TM17 mutants of multidrug resistance protein 1 (ABCC1)."

No. Sentence Comment

3 Here we have extended our characterization of mutants K332L and W1246C to further define the different roles these two residues play in determining the substrate and inhibitor specificity of MRP1. Login to comment
7 Finally, the differing abilities of the cysteinyl leukotriene derivatives leukotriene C4, D4, and F4 to inhibit estradiol glucuronide transport by wild-type and K332L mutant MRP1 provide further evidence that TM6-Lys332 is involved in the recognition of the ␥-Glu portion of substrates and modulators containing GSH or GSH-like moieties. Login to comment
36 B-E, ATP-dependent uptake of 3 H-labeled organic anions was measured in membrane vesicles prepared from HEK293T (HEK) cells transfected with wild-type MRP1 (shaded bar) and K332L and W1246C mutant (open bars) cDNAs as described under Materials and Methods. Login to comment
57 The generation of wild-type, K332L, and W1246C mutant MRP1 pcDNA3.1 expression constructs has been described previously (Ito et al., 2001a; Haimeur et al., 2002). Login to comment
85 Equilibrium binding of [3 H]estrone 3-sulfate to wild-type MRP1 and the K332L and W1246C mutants was determined as described previously (Rothnie et al., 2006, 2008). Login to comment
91 To investigate the effect of estrone 3-sulfate concentration on [3 H]estrone 3-sulfate binding, 10 ␮g of membrane protein from wild-type and mutant MRP1-transfected cells were incubated with various concentrations of [3 H]estrone 3-sulfate (50 nM to 10 ␮M) and 3 mM S-MeGSH in the presence or absence of the competitive substrates E217betaG (1 mM) in the case of the K332L mutant and LTC4 (10 ␮M) in the case of the W1246C mutant. Login to comment
95 In the first series of experiments, the ability of the K332L and W1246C mutants to transport methotrexate and estrone 3-sulfate (in the presence of GSH and S-MeGSH) was measured. Login to comment
96 After transfecting HEK293T cells with the wild-type and mutant constructs, membrane vesicles were prepared, and relative expression levels of the K332L and W1246C mutants were determined by immunoblotting and found to be similar to wild-type MRP1 (data not shown), as reported previously (Ito et al., 2001a; Haimeur et al., 2002). Login to comment
98 As shown in Fig. 1B, uptake of [3 H]methotrexate by the K332L mutant was comparable with wild-type MRP1, whereas uptake by W1246C was reduced by Ͼ75%. Login to comment
100 As reported previously (Ito et al., 2001a; Haimeur et al., 2002), [3 H]LTC4 transport by the K332L mutant was also comparable with the untransfected HEK293T negative control, whereas that of the W1246C mutant was similar to wild-type MRP1 (Fig. 1D). Login to comment
101 On the other hand, the K332L mutant transported [3 H]E217betaG at levels comparable with wild-type MRP1, whereas the W1246C mutant showed no detectable transport of this conjugated estrogen, as expected from previous studies (Ito et al., 2001a) (Fig. 1E). Login to comment
102 S-MeGSH Fails to Increase Estrone 3-Sulfate Binding to the K332L and W1246C Mutants. Login to comment
103 To determine whether changes in the ability of S-MeGSH to stimulate binding might contribute to the low levels of estrone 3-sulfate transport displayed by the K332L and W1246C mutants, equilibrium binding assays with MRP1 in the nucleotide-free state were carried out. Login to comment
107 In contrast, S-MeGSH had little or no effect on estrone 3-sulfate binding to the K332L (Fig. 2A) or W1246C (Fig. 2B) mutants. Login to comment
108 The EC50 for S-MeGSH of wild-type MRP1 was 1.24 Ϯ 0.07 mM, whereas the binding curves for the K332L and W1246C mutants were almost flat, precluding reliable estimations of their EC50s for this tripeptide. Login to comment
109 Estrone 3-sulfate binding values for both the K332L and W1246C mutants at apparent saturation were just 20% that of wild-type MRP1 (after subtraction of nonspecific binding). Login to comment
110 To exclude the possibility that S-MeGSH-stimulated estrone 3-sulfate binding to the K332L and W1246C mutants might be underestimated in the above experiments because the initial concentration of estrone 3-sulfate used (50 nM) was too low, the binding assays were repeated at higher concentrations of this conjugated estrogen. Login to comment
112 K332L Decreases Ability of S-MeGSH to Stimulate Estrone 3-Sulfate Uptake, Whereas W1246C Decreases Affinity for Estrone 3-Sulfate. Login to comment
114 S-MeGSH stimulated binding of [3 H]estrone 3-sulfate by MRP1 mutants K332L and W1246C. Login to comment
115 A, binding of [3 H]estrone 3-sulfate (50 nM) to wild-type MRP1 (f), K332L mutant (F), and control HEK (E) membranes (10 ␮g of protein) was measured at 23°C for 60 min in the presence of increasing concentrations (0.01-18 mM) of S-MeGSH. Login to comment
119 C, specific binding of [3 H]estrone 3-sulfate to wild-type MRP1 (f), W1246C (Œ), K332L (F), and control HEK (E) membranes (10 ␮g of protein) was measured at estrone 3-sulfate concentrations ranging from 0.01 to 10 mM in the presence of 3 mM S-MeGSH. Login to comment
123 To help distinguish between these possibilities, ATP-dependent estrone 3-sulfate transport by the K332L and W1246C mutants was measured in the absence of S-MeGSH (or GSH) and compared with transport by wild-type MRP1. Login to comment
124 As shown in Fig. 3A, [3 H]estrone 3-sulfate uptake in the absence of S-MeGSH (or GSH) by K332L was similar to that of wild-type MRP1. Login to comment
127 These observations indicate that like wild-type MRP1, the K332L mutant can still bind and transport estrone 3-sulfate in the absence of S-MeGSH (or GSH), but unlike wild-type MRP1, estrone 3-sulfate uptake by the K332L mutant is no longer stimulated by S-MeGSH. Login to comment
128 Conversely, unlike wild-type and K332L mutant MRP1, W1246C apparently no longer binds estrone 3-sulfate; thus, no transport is observed in either the presence or absence of S-MeGSH (or GSH). Login to comment
129 Loss of Synergistic Inhibition of E217betaG Uptake by GSH and Apigenin for the K332L Mutant. Login to comment
131 Therefore, we reasoned that if the K332L mutant could no longer bind GSH (or S-MeGSH), then GSH (or S-MeGSH) would no longer be expected to act synergistically with apigenin to inhibit uptake of LTC4 or other organic anion substrates. Login to comment
132 Accordingly, ATP-dependent E217betaG uptake by K332L-enriched membrane vesicles was measured in the absence or presence of GSH (3 mM) and apigenin (10 ␮M). Login to comment
135 In contrast, neither GSH or apigenin (10 ␮M) alone nor the combination of GSH and apigenin had any effect on E217betaG uptake by the K332L mutant. Login to comment
137 Because higher concentrations of apigenin (30 ␮M) inhibited E217betaG transport by wild-type and K332L MRP1 similarly (data not shown), these observations support the conclusion that GSH (and S-MeGSH) binding to the K332L mutant is severely impaired. Login to comment
138 Effect of MRP1 Modulators on the Activity of MRP1 Mutants K332L and W1246C. Login to comment
139 Because of the marked differences in the substrate specificity of the K332L and W1246C mutants, we next investigated whether the two mutants differed in their sensitivity to compounds reported previously to be modulators of MRP1 transport activity. Login to comment
140 Thus, the effect of four small molecule inhibitors (MK571, LY465803, LY171883, and BAY u9773) (Fig. 4A) and two GSH derivatives (S-decyl-GSH and GSSG) (Fig. 4B) were tested for their ability to inhibit E217betaG transport by the K332L mutant. Login to comment
145 As summarized in Table 1 and shown in Fig. 5, MK571 and LY171883 were moderately (2-fold) less potent inhibitors of E217betaG uptake by wild-type MRP1 than by the K332L mutant, whereas the inhibitory potency of BAYu9773 was not significantly different for the mutant and wild-type transporters. Login to comment
146 In contrast, LY465803 (ϩGSH) showed a far greater potency (16-fold) to inhibit wild-type compared with K332L mutant MRP1. Login to comment
147 In a similar manner, the GSH derivative S-decyl-GSH and GSSG inhibited wild-type MRP1 activity with IC50s Ͼ100-fold and Ͼ30-fold lower than for K332L, respectively. Login to comment
148 In contrast to its more potent inhibitory effect on E217betaG transport by the K332L mutant, MK571 was a less potent inhibitor (ϳ3-fold) of LTC4 transport by the W1246C mutant than by wild-type MRP1 (Table 2; Fig. 6A). Login to comment
149 However, similar to K332L, the inhibitory potency of BAY u9773 for LTC4 transport by wild-type and W1246C was comparable (Table 2; Fig. 6B). Login to comment
150 Also similar to K332L, LY465803 (ϩGSH) showed a far greater (Ͼ250-fold) potency to inhibit wild-type MRP1 than the W1246C mutant (Table 2; Fig. 6C). Login to comment
151 Finally, in contrast to K332L, the sensitivity of W1246C and wild-type MRP1 to FIG. 3. Login to comment
152 [3 H]Estrone 3-sulfate and [3 H]E217betaG vesicular uptake by K332L and W1246C mutant and wild-type MRP1 proteins. Login to comment
153 A, ATP-dependent [3 H]estrone 3-sulfate uptake by membrane vesicles prepared from untransfected control cells (HEK) (solid bar) and cells transfected with cDNA vectors containing wild-type MRP1 (shaded bar), and K332L and W1246C mutant MRP1 (open bars) was measured in the absence of S-MeGSH. Login to comment
154 Inset, [3 H]estrone 3-sulfate uptake by membrane vesicles prepared from untransfected HEK cells (solid bars) and HEK cells expressing comparable levels of wild-type MRP1 (shaded bars), and MRP1 mutants K332L and W1246C (open bars) was measured in the absence and presence of S-MeGSH as described under Materials and Methods. Login to comment
157 B, ATP-dependent [3 H]E217betaG uptake was measured in membrane vesicles prepared from untransfected cells (HEK) (solid bars), and wild-type MRP1 (shaded bars), and K332L-MRP1 (open bars) transfected cells with and without GSH (3 mM) and with and without apigenin (10 ␮M) as indicated. Login to comment
160 Effect of Leukotriene Derivatives on E217betaG Transport Activity by K332L. Login to comment
162 Thus, the equal sensitivity of the transport activities of the K332L and W1246C mutants to inhibition by BAY u9773, despite their profoundly different abilities to transport LTC4, suggests that the K332L mutant has lost its ability to bind to the GSH moiety of LTC4. Login to comment
163 To determine whether this loss of binding involves one or more of the three amino acids that comprise the GSH moiety of LTC4, E217betaG transport assays with wild-type MRP1 and the K332L mutant were carried out in the presence of various concentrations of the cysteinyl leukotriene derivatives LTC4, LTD4, and LTF4. Login to comment
164 As expected from previous studies (Haimeur et al., 2002), the IC50 of LTC4 (containing ␥-Glu, Cys, and Gly) of the K332L mutant was significantly increased (ϳ25-fold) compared with that of wild-type MRP1 (Table 3; Fig. 7A). Login to comment
165 When E217betaG transport was carried out in the presence of LTD4 (lacking a ␥-Glu moiety but containing Gly and Cys), the IC50s of wild-type MRP1 and the K332L mutant were the same, although the inhibitor potency of LTD4 compared with LTC4 was ϳ40-fold less for wild-type MRP1 but just ϳ2-fold less for K332L (Table 3; Fig. 7B). Login to comment
166 The IC50s of LTF4 (containing a ␥-Glu moiety but lacking Gly) for K332L and wild-type MRP1 differed by 4-fold, with the inhibitor potency of LTF4 comparable with LTD4 (Table 3; Fig. 7C). Login to comment
167 Thus, the K332L mutant protein is considerably less sensitive than wild-type MRP1 with respect to inhibition by the ␥-Glu-containing LTC4 and LTF4 but not the ␥-Glu-less LTD4, suggesting that Lys332 is critical for recognizing the ␥-Glu moiety of GSH. Login to comment
168 TABLE 1 Effect of modulators on E217betaG uptake by wild-type and K332L mutant MRP1 The values shown represent the means (ϮS.D.) of IC50 values obtained in three independent experiments. Login to comment
170 E217betaG Uptake IC50 Modulator Wild-type K332L ␮M ␮M MK571 0.4 Ϯ 0.1 0.20 Ϯ 0.07a LY171883 19.8, 14.7 8.8, 8.1 BAY u9773 0.20 Ϯ 0.03 0.3 Ϯ 0.1 LY465803 (ϩGSH) 0.2 Ϯ 0.1 3.3 Ϯ 2.5b S-Decyl-GSH 0.07 Ϯ 0.01 Ͼ10, Ͼ10c GSSG 16.3, 13.0 503.0, 505.8 a Significantly different from IC50 obtained with wild-type MRP1 (p Ͻ 0.05). Login to comment
180 In the present study, we have further characterized the substrate specificity of two of these, the TM6 mutant K332L and the TM17 mutant W1246C, and have also determined their inhibitor profiles. Login to comment
189 Effect of MRP1 modulators and GSH derivatives on [3 H]E217betaG transport by wild-type and K332L mutant MRP1. ATP-dependent vesicular uptake of [3 H]E217betaG by wild-type MRP1 (open symbols, dotted lines) and K332L mutant MRP1 (closed symbols, solid lines) was measured in the presence of the indicated concentrations of modulators and GSH derivatives. Login to comment
198 However, this was not the case for membranes prepared from transfected HEK cells expressing either the K332L or W1246C mutants. Login to comment
200 We found that GSH-independent estrone 3-sulfate transport by W1246C was similar to negative controls, whereas transport by K332L was comparable with wild-type MRP1. Login to comment
201 Thus, in the case of the K332L mutant, impaired GSH-stimulated estrone 3-sulfate transport seems to be caused by a loss of GSH binding. Login to comment
203 Furthermore, unlike wild-type MRP1, GSH no longer acted synergistically with apigenin to inhibit E217betaG uptake by the K332L mutant. Login to comment
205 The latter conclusion is also consistent with the inhibitor profile displayed by the K332L mutant (Table 1; Fig. 5). Login to comment
206 The inhibitory potencies of modulators such as MK571, LY171883, and BAY u9773, which do not contain a GSH moiety and are not GSH-dependent, on the transport activities of wild-type and K332L mutant MRP1 were much more similar (1.5-2-fold difference in IC50s) than those of modulators that contain a GSH or GSH-like moiety (S-decyl-GSH, GSSG) or are dependent on GSH (LY465803) for their activity (15-30-fold difference in IC50s). Login to comment
213 When transport assays were carried out in the presence of three cysteinyl leukotriene derivatives to determine whether reduced binding of compounds that contain GSH-like moieties by the K332L mutant involves one or more of the three amino acids that comprise FIG. 6. Login to comment
219 TABLE 3 Effect of leukotriene derivatives on E217betaG uptake by wild-type and K332L mutant MRP1 The values shown represent the means (ϮS.D.) of IC50 values obtained in three or four independent experiments (number shown in parentheses). Login to comment
220 E217betaG Uptake IC50 Leukotriene Derivative Wild-type K332L ␮M ␮M LTC4 0.1 Ϯ 0.03 (3) 2.5 Ϯ 0.5 (3)a LTD4 4.3 Ϯ 0.4 (3) 4.2 Ϯ 2.3 (3) LTF4 3.7 Ϯ 0.1 (4) 15.3 Ϯ 7.3 (4)a a Significantly different from IC50 in wild-type MRP1 (p Ͻ 0.01). Login to comment
222 Thus, E217betaG transport by the K332L mutant was considerably less sensitive than wild-type MRP1 to inhibition by the ␥-Glu- containing LTC4 and LTF4 (25- and 4-fold differences in IC50s, respectively) than for the ␥-Glu-less LTD4, for which the IC50s were the same (Fig. 7; Table 3). Login to comment
229 In conclusion, we have extended our characterization of the MRP1 mutants K332L and W1246C and further defined the different roles of these two amino acids in determining the substrate and inhibitor specificity of MRP1. Login to comment

PMID: 19949927 [PubMed] Chang XB et al: "Molecular mechanism of ATP-dependent solute transport by multidrug resistance-associated protein 1."

No. Sentence Comment

104 Mutations of C43S in TM1 (112); P343A, K332L and K332D in TM6 (113, 114); W445A and P448A in TM8 (113, 115); T550A, T556A and P557A in TM10 (113, 116); N590A, F594A, P595A, N597A, S604A and S605A in TM11 (113, 117, 118); E1089Q, E1089A, E1089L, E1089N, K1092, S1097 and N1100 in TM14 (119, 120); R1197K in TM16 (121); Y1236F, T1241A, T1242A, T1242C, T1242S, T1242L, Y1243F, N1245A, W1246C, W1246A, W1246F, W1246Y or R1249K in TM17 (121-124) significantly affect MRP1 function. Login to comment

PMID: 21143116 [PubMed] He SM et al: "Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1)."

No. Sentence Comment

765 Both Lys332Leu and Trp1246Cys mutants were as sensitive as wild-type MRP1/ABCC1 to MK-571, LY171883, and the potent MRP1/ABCC1 inhibitor 6-[4 -carboxyphenylthio]-5[S]- hydroxy-7[E], 11[Z]14[Z]-eicosatetrenoic acid (BAY u9773, a leukotriene-like dual antagonist that acts on both CysLT1 and CysLT2 receptors) [341]. Login to comment
766 MK-571 and LY171883 were moderately (2-fold) less potent inhibitors of E217 G uptake by wild-type MRP1/ABCC1 than by the Lys332Leu mutant, but LY465803 showed 16-fold greater potency to inhibit wild-type compared with Lys332Leu mutant. Login to comment
767 In a similar manner, the GSH derivative S-decyl-GSH and GSSG inhibited wild-type MRP1/ABCC1 activity with IC50 >100-fold and >30-fold lower than for Lys332Leu, respectively [341]. Login to comment
768 In contrast to its more potent inhibitory effect on E217 G transport by the Lys332Leu mutant, MK-571 was a less potent inhibitor ( 3-fold) of LTC4 transport by the Trp1246Cys mutant than by wild-type MRP1. Login to comment
769 However, similar to Lys332Leu, the inhibitory potency of BAY u9773 for LTC4 transport by wild-type and Trp1246Cys was comparable. Login to comment