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result sql = Kinetics of glutathione and daunorubicin efflux from multidrug resistance protein overexpressing small-cell lung cancer cells.
Kinetics of glutathione and daunorubicin efflux from multidrug resistance protein overexpressing small-cell lung cancer cells.
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char = e;code = 101
char = l;code = 108
char = i;code = 105
char = s;code = 115
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char = M;code = 77
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char = n;code = 110
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = r;code = 114
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char = v;code = 118
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = d;code = 100
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char = a;code = 97
char = ;code = 32
char = K;code = 75
char = m;code = 109
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 3;code = 51
char = .;code = 46
char = 4;code = 52
char = +;code = 43
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char = -;code = 45
char = 1;code = 49
char = .;code = 46
char = 4;code = 52
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char = m;code = 109
char = M;code = 77
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = V;code = 86
char = m;code = 109
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = .;code = 46
char = 5;code = 53
char = +;code = 43
char = /;code = 47
char = -;code = 45
char = 0;code = 48
char = .;code = 46
char = 2;code = 50
char = x;code = 120
char = 1;code = 49
char = 0;code = 48
char = (;code = 40
char = -;code = 45
char = 1;code = 49
char = 8;code = 56
char = );code = 41
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = /;code = 47
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = /;code = 47
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = A;code = 65
char = T;code = 84
char = P;code = 80
char = -;code = 45
char = d;code = 100
char = e;code = 101
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char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 3;code = 51
char = -;code = 45
char = (;code = 40
char = [;code = 91
char = [;code = 91
char = 3;code = 51
char = -;code = 45
char = (;code = 40
char = 2;code = 50
char = -;code = 45
char = [;code = 91
char = 7;code = 55
char = -;code = 45
char = c;code = 99
char = h;code = 104
char = l;code = 108
char = o;code = 111
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = 2;code = 50
char = -;code = 45
char = q;code = 113
char = u;code = 117
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = ];code = 93
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = );code = 41
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = ];code = 93
char = -;code = 45
char = [;code = 91
char = (;code = 40
char = 3;code = 51
char = -;code = 45
char = d;code = 100
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = -;code = 45
char = 3;code = 51
char = -;code = 45
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = y;code = 121
char = l;code = 108
char = );code = 41
char = -;code = 45
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
char = ];code = 93
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = ];code = 93
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
char = );code = 41
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = K;code = 75
char = 5;code = 53
char = 7;code = 55
char = 1;code = 49
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 5;code = 53
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = b;code = 98
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 1;code = 49
char = .;code = 46
char = 4;code = 52
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = ;code = 32
char = M;code = 77
char = K;code = 75
char = 5;code = 53
char = 7;code = 55
char = 1;code = 49
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = M;code = 77
char = R;code = 82
char = P;code = 80
char = 1;code = 49
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = A;code = 65
char = T;code = 84
char = P;code = 80
char = -;code = 45
char = d;code = 100
char = e;code = 101
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char = e;code = 101
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char = d;code = 100
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char = t;code = 116
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char = a;code = 97
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char = s;code = 115
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = u;code = 117
char = n;code = 110
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char = r;code = 114
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
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char = n;code = 110
char = d;code = 100
char = e;code = 101
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char = i;code = 105
char = t;code = 116
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char = s;code = 115
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char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = s;code = 115
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
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char = ;code = 32
char = d;code = 100
char = a;code = 97
char = u;code = 117
char = n;code = 110
char = o;code = 111
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char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
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char = b;code = 98
char = e;code = 101
char = c;code = 99
char = a;code = 97
char = m;code = 109
char = e;code = 101
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char = s;code = 115
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = d;code = 100
char = a;code = 97
char = u;code = 117
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
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char = n;code = 110
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = s;code = 115
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = 5;code = 53
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char = m;code = 109
char = M;code = 77
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = a;code = 97
char = u;code = 117
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = W;code = 87
char = E;code = 69
char = ;code = 32
char = W;code = 87
char = E;code = 69
char = R;code = 82
char = E;code = 69
char = ;code = 32
char = T;code = 84
char = H;code = 72
char = E;code = 69
char = R;code = 82
char = E;code = 69
char = F;code = 70
char = O;code = 79
char = R;code = 82
char = E;code = 69
char = ;code = 32
char = I;code = 73
char = N;code = 78
char = ;code = 32
char = T;code = 84
char = H;code = 72
char = E;code = 69
char = ;code = 32
char = S;code = 83
char = I;code = 73
char = T;code = 84
char = U;code = 85
char = A;code = 65
char = T;code = 84
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = ;code = 32
char = W;code = 87
char = H;code = 72
char = E;code = 69
char = R;code = 82
char = E;code = 69
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = A;code = 65
char = C;code = 67
char = T;code = 84
char = E;code = 69
char = D;code = 68
char = ;code = 32
char = A;code = 65
char = S;code = 83
char = ;code = 32
char = A;code = 65
char = N;code = 78
char = ;code = 32
char = A;code = 65
char = C;code = 67
char = T;code = 84
char = I;code = 73
char = V;code = 86
char = A;code = 65
char = T;code = 84
char = O;code = 79
char = R;code = 82
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char = <;code = 60
char = /;code = 47
char = b;code = 98
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char = ;code = 32
char = i;code = 105
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char = p;code = 112
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char = w;code = 119
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char = s;code = 115
char = a;code = 97
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char = y;code = 121
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char = p;code = 112
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char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
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char = y;code = 121
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char = M;code = 77
char = R;code = 82
char = P;code = 80
char = 1;code = 49
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
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char = a;code = 97
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char = p;code = 112
char = o;code = 111
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char = i;code = 105
char = d;code = 100
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char = g;code = 103
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char = r;code = 114
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char = s;code = 115
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char = s;code = 115
char = t;code = 116
char = a;code = 97
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char = c;code = 99
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = o;code = 111
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = g;code = 103
char = a;code = 97
char = v;code = 118
char = e;code = 101
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char = h;code = 104
char = a;code = 97
char = l;code = 108
char = f;code = 102
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char = t;code = 116
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char = m;code = 109
char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
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result sql = The present study examined how the multidrug resistance protein (MRP1), which is an ATP-dependent anionic conjugate transporter, also mediates the transport of reduced glutathione (GSH) and the co-transport of the cationic drug, daunorubicin, with GSH in living GLC4/Adr cells. To obtain information on the affinity of GSH for the multidrug resistance protein in GLC4/Adr cells, we investigated the GSH concentration dependence of the ATP-dependent GSH efflux. The intracellular GSH concentration was modulated by preincubation of the cells with 25 microM buthionine sulfoximine, an inhibitor of GSH synthetase, for 0-24 h. The transport of GSH was related to the intracellular GSH concentration up to approximately 5 mM and then plateaued. Fitting of the obtained data according to the Michaelis-Menten equation revealed a Km of 3.4+/-1.4 mM and a Vmax of 1.5+/-0.2x10(-18) mol/cell/s. The ATP-dependent transport of GSH was inhibited by 3-([[3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl]-[(3-dimethylamino-3-oxopropyl)-thio]-methyl]thio)propanoic acid (MK571), with 50% inhibition being obtained with 1.4 microM MK571. We investigated the GSH concentration dependence of the MRP1-mediated ATP-dependent transport of daunorubicin under conditions where the transport of daunorubicin became saturated. The daunorubicin transport was related to the intracellular GSH concentration up to approximately 5 mM and then plateaued. WE WERE THEREFORE IN THE SITUATION WHERE GSH ACTED AS AN ACTIVATOR: its presence was necessary for the binding and transport of daunorubicin by MRP1. However, GSH was also transported by the multidrug resistance protein. The concentration of GSH that gave half the maximal rate of daunorubicin efflux was 2.1+/-0.8 mM, very similar to the Km value obtained for GSH. In conclusion, the rate of daunorubicin efflux, under conditions where the transport of daunorubicin became saturated, and the rate of GSH efflux determined at any intracellular concentration of GSH were very similar, yielding a 1:1 stoichiometry with respect to GSH and daunorubicin transport. These results support a model in which daunorubicin is co-transported with GSH.

Publication: Eur. J. Pharmacol. 2001 Jun 1 ;421(1)::1-9.
Publication Date: 2001 Jun 1
Study Author(s): Salerno, M;Garnier-Suillerot, A;
Institution: Laboratoire de Physicochimie Biomoléculaire et Cellulaire, ESA CNRS 7033, Université Paris Nord, 74 rue Marcel Cachin, 93017, Bobigny, France.
Shortcut link to this study:
The present study examined how the multidrug resistance protein (MRP1), which is an ATP-dependent anionic conjugate transporter, also mediates the transport of reduced glutathione (GSH) and the co-transport of the cationic drug, daunorubicin, with GSH in living GLC4/Adr cells. To obtain information on the affinity of GSH for the multidrug resistance protein in GLC4/Adr cells, we investigated the GSH concentration dependence of the ATP-dependent GSH efflux. The intracellular GSH concentration was modulated by preincubation of the cells with 25 microM buthionine sulfoximine, an inhibitor of GSH synthetase, for 0-24 h. The transport of GSH was related to the intracellular GSH concentration up to approximately 5 mM and then plateaued. Fitting of the obtained data according to the Michaelis-Menten equation revealed a Km of 3.4+/-1.4 mM and a Vmax of 1.5+/-0.2x10(-18) mol/cell/s. The ATP-dependent transport of GSH was inhibited by 3-([[3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl]-[(3-dimethylamino-3-oxopropyl)-thio]-methyl]thio)propanoic acid (MK571), with 50% inhibition being obtained with 1.4 microM MK571. We investigated the GSH concentration dependence of the MRP1-mediated ATP-dependent transport of daunorubicin under conditions where the transport of daunorubicin became saturated. The daunorubicin transport was related to the intracellular GSH concentration up to approximately 5 mM and then plateaued. WE WERE THEREFORE IN THE SITUATION WHERE GSH ACTED AS AN ACTIVATOR: its presence was necessary for the binding and transport of daunorubicin by MRP1. However, GSH was also transported by the multidrug resistance protein. The concentration of GSH that gave half the maximal rate of daunorubicin efflux was 2.1+/-0.8 mM, very similar to the Km value obtained for GSH. In conclusion, the rate of daunorubicin efflux, under conditions where the transport of daunorubicin became saturated, and the rate of GSH efflux determined at any intracellular concentration of GSH were very similar, yielding a 1:1 stoichiometry with respect to GSH and daunorubicin transport. These results support a model in which daunorubicin is co-transported with GSH.
PMID: 11408043

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