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result sql = L-Lactate, D-lactate, propionate and acetate (all 20 mM) caused a marked intracellular acidification in HIT-T15 cells loaded with 2'7'-bis(carboxyethyl)-5'(6')-carboxyfluorescein (BCECF), followed by recovery to more alkaline values. The effects of L- and D-lactate, but not propionate or acetate, were inhibited by 5 mM alpha-fluorocinnamate. Both L- and D-lactate caused a marked depolarisation and rise in cytosolic [Ca2+] in HIT cells as assessed by oxonol-V and quin2 fluorescence, respectively. Propionate had similar, though less marked, effects, whereas acetate exerted only a modest influence on membrane potential and cytosolic [Ca2+]. The rate of oxidation of L-lactate by HIT cells greatly exceeded that of D-lactate. alpha-Fluorocinnamate delayed, but did not prevent, the effects of L-lactate on HIT cell membrane potential or cytosolic [Ca2+]. L-lactate diminished the rate of efflux of 86Rb+ from preloaded HIT cells. Inhibition of calcium- and nucleotide-sensitive K+ channels with tetraethylammonium and tolbutamide also reduced the 86Rb+ efflux rate, and prevented any further reduction in response to L-lactate. However, such inhibition of K+ channels did not prevent a further depolarisation and rise in cytosolic [Ca2+] upon the subsequent addition of lactate. It is suggested that the activation of HIT-T15 cells by lactate is not the result of intracellular acidification or increased metabolic flux, and does not require diminished K+ permeability. An alternative mechanism is based upon the possible electrogenic flux of lactate across the plasma membrane.
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result sql = Studies of the mechanism of activation of HIT-T15 cells by lactate.
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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 = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = H;code = 72
char = I;code = 73
char = T;code = 84
char = -;code = 45
char = T;code = 84
char = 1;code = 49
char = 5;code = 53
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = a;code = 97
char = d;code = 100
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 = 2;code = 50
char = ';code = 39
char = 7;code = 55
char = ';code = 39
char = -;code = 45
char = b;code = 98
char = i;code = 105
char = s;code = 115
char = (;code = 40
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = );code = 41
char = -;code = 45
char = 5;code = 53
char = ';code = 39
char = (;code = 40
char = 6;code = 54
char = ';code = 39
char = );code = 41
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = c;code = 99
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = B;code = 66
char = C;code = 67
char = E;code = 69
char = C;code = 67
char = F;code = 70
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = k;code = 107
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = e;code = 101
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 = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = D;code = 68
char = -;code = 45
char = l;code = 108
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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 = 5;code = 53
char = ;code = 32
char = m;code = 109
char = M;code = 77
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = -;code = 45
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = n;code = 110
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = D;code = 68
char = -;code = 45
char = l;code = 108
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = [;code = 91
char = C;code = 67
char = a;code = 97
char = 2;code = 50
char = +;code = 43
char = ];code = 93
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = H;code = 72
char = I;code = 73
char = T;code = 84
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = -;code = 45
char = V;code = 86
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = q;code = 113
char = u;code = 117
char = i;code = 105
char = n;code = 110
char = 2;code = 50
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = s;code = 115
char = t;code = 116
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char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = [;code = 91
char = C;code = 67
char = a;code = 97
char = 2;code = 50
char = +;code = 43
char = ];code = 93
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
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 = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = l;code = 108
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = H;code = 72
char = I;code = 73
char = T;code = 84
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = c;code = 99
char = e;code = 101
char = e;code = 101
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = D;code = 68
char = -;code = 45
char = l;code = 108
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = -;code = 45
char = F;code = 70
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = n;code = 110
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = y;code = 121
char = e;code = 101
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = l;code = 108
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = H;code = 72
char = I;code = 73
char = T;code = 84
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = [;code = 91
char = C;code = 67
char = a;code = 97
char = 2;code = 50
char = +;code = 43
char = ];code = 93
char = .;code = 46
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = l;code = 108
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = h;code = 104
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 = 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 = e;code = 101
char = f;code = 102
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = x;code = 120
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 8;code = 56
char = 6;code = 54
char = R;code = 82
char = b;code = 98
char = +;code = 43
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = a;code = 97
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = H;code = 72
char = I;code = 73
char = T;code = 84
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
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
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = -;code = 45
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = -;code = 45
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = K;code = 75
char = +;code = 43
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
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char = c;code = 99
char = t;code = 116
char = a;code = 97
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char = e;code = 101
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char = t;code = 116
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char = i;code = 105
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char = ;code = 32
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char = t;code = 116
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char = ;code = 32
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char = t;code = 116
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char = c;code = 99
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char = e;code = 101
char = ;code = 32
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char = o;code = 111
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = f;code = 102
char = l;code = 108
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char = t;code = 116
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result sql = L-Lactate, D-lactate, propionate and acetate (all 20 mM) caused a marked intracellular acidification in HIT-T15 cells loaded with 2'7'-bis(carboxyethyl)-5'(6')-carboxyfluorescein (BCECF), followed by recovery to more alkaline values. The effects of L- and D-lactate, but not propionate or acetate, were inhibited by 5 mM alpha-fluorocinnamate. Both L- and D-lactate caused a marked depolarisation and rise in cytosolic [Ca2+] in HIT cells as assessed by oxonol-V and quin2 fluorescence, respectively. Propionate had similar, though less marked, effects, whereas acetate exerted only a modest influence on membrane potential and cytosolic [Ca2+]. The rate of oxidation of L-lactate by HIT cells greatly exceeded that of D-lactate. alpha-Fluorocinnamate delayed, but did not prevent, the effects of L-lactate on HIT cell membrane potential or cytosolic [Ca2+]. L-lactate diminished the rate of efflux of 86Rb+ from preloaded HIT cells. Inhibition of calcium- and nucleotide-sensitive K+ channels with tetraethylammonium and tolbutamide also reduced the 86Rb+ efflux rate, and prevented any further reduction in response to L-lactate. However, such inhibition of K+ channels did not prevent a further depolarisation and rise in cytosolic [Ca2+] upon the subsequent addition of lactate. It is suggested that the activation of HIT-T15 cells by lactate is not the result of intracellular acidification or increased metabolic flux, and does not require diminished K+ permeability. An alternative mechanism is based upon the possible electrogenic flux of lactate across the plasma membrane.
Publication: Biochim. Biophys. Acta 1991 Jan 31 ;1091(2)::141-4.
Publication Date: 1991 Jan 31
Study Author(s): Lynch, A M;Trebilcock, R;Tomlinson, S;Best, L;
Institution: Department of Medicine, University of Manchester, U.K.
Shortcut link to this study:
Publication Date: 1991 Jan 31
Study Author(s): Lynch, A M;Trebilcock, R;Tomlinson, S;Best, L;
Institution: Department of Medicine, University of Manchester, U.K.
Shortcut link to this study:
L-Lactate, D-lactate, propionate and acetate (all 20 mM) caused a marked intracellular acidification in HIT-T15 cells loaded with 2'7'-bis(carboxyethyl)-5'(6')-carboxyfluorescein (BCECF), followed by recovery to more alkaline values. The effects of L- and D-lactate, but not propionate or acetate, were inhibited by 5 mM alpha-fluorocinnamate. Both L- and D-lactate caused a marked depolarisation and rise in cytosolic [Ca2+] in HIT cells as assessed by oxonol-V and quin2 fluorescence, respectively. Propionate had similar, though less marked, effects, whereas acetate exerted only a modest influence on membrane potential and cytosolic [Ca2+]. The rate of oxidation of L-lactate by HIT cells greatly exceeded that of D-lactate. alpha-Fluorocinnamate delayed, but did not prevent, the effects of L-lactate on HIT cell membrane potential or cytosolic [Ca2+]. L-lactate diminished the rate of efflux of 86Rb+ from preloaded HIT cells. Inhibition of calcium- and nucleotide-sensitive K+ channels with tetraethylammonium and tolbutamide also reduced the 86Rb+ efflux rate, and prevented any further reduction in response to L-lactate. However, such inhibition of K+ channels did not prevent a further depolarisation and rise in cytosolic [Ca2+] upon the subsequent addition of lactate. It is suggested that the activation of HIT-T15 cells by lactate is not the result of intracellular acidification or increased metabolic flux, and does not require diminished K+ permeability. An alternative mechanism is based upon the possible electrogenic flux of lactate across the plasma membrane.
PMID: 1995073
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