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result sql = Anti-calmodulins and tricyclic adjuvants in pain therapy block the TRPV1 channel.
Anti-calmodulins and tricyclic adjuvants in pain therapy block the TRPV1 channel.
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char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = o;code = 111
char = p;code = 112
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 = 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 = ;code = 32
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = (;code = 40
char = 2;code = 50
char = +;code = 43
char = );code = 41
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = m;code = 109
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
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 = ;code = 32
char = p;code = 112
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = r;code = 114
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 = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ,;code = 44
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 = s;code = 115
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = (;code = 40
char = 2;code = 50
char = +;code = 43
char = );code = 41
char = -;code = 45
char = u;code = 117
char = p;code = 112
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = P;code = 80
char = V;code = 86
char = 1;code = 49
char = (;code = 40
char = +;code = 43
char = );code = 41
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 = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = x;code = 120
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 = s;code = 115
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
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
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = P;code = 80
char = V;code = 86
char = 1;code = 49
char = (;code = 40
char = +;code = 43
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = g;code = 103
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = l;code = 108
char = i;code = 105
char = a;code = 97
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 = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = p;code = 112
char = s;code = 115
char = y;code = 121
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = z;code = 122
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = s;code = 115
char = t;code = 116
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 = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = (;code = 40
char = 2;code = 50
char = +;code = 43
char = );code = 41
char = -;code = 45
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = e;code = 101
char = t;code = 116
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 = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = P;code = 80
char = V;code = 86
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = x;code = 120
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 = s;code = 115
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = (;code = 40
char = 2;code = 50
char = +;code = 43
char = );code = 41
char = -;code = 45
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 = 46
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = -;code = 45
char = e;code = 101
char = v;code = 118
char = o;code = 111
char = k;code = 107
char = e;code = 101
char = d;code = 100
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
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = P;code = 80
char = V;code = 86
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = M;code = 77
char = D;code = 68
char = A;code = 65
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = /;code = 47
char = C;code = 67
char = a;code = 97
char = (;code = 40
char = 2;code = 50
char = +;code = 43
char = );code = 41
char = -;code = 45
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 = a;code = 97
char = s;code = 115
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = a;code = 97
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 = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
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 = m;code = 109
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = z;code = 122
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
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result sql = Ca(2+)-loaded calmodulin normally inhibits multiple Ca(2+)-channels upon dangerous elevation of intracellular Ca(2+) and protects cells from Ca(2+)-cytotoxicity, so blocking of calmodulin should theoretically lead to uncontrolled elevation of intracellular Ca(2+). Paradoxically, classical anti-psychotic, anti-calmodulin drugs were noted here to inhibit Ca(2+)-uptake via the vanilloid inducible Ca(2+)-channel/inflamatory pain receptor 1 (TRPV1), which suggests that calmodulin inhibitors may block pore formation and Ca(2+) entry. Functional assays on TRPV1 expressing cells support direct, dose-dependent inhibition of vanilloid-induced (45)Ca(2+)-uptake at microM concentrations: calmidazolium (broad range) > or = trifluoperazine (narrow range) chlorpromazine/amitriptyline>fluphenazine>W-7 and W-13 (only partially). Most likely a short acidic domain at the pore loop of the channel orifice functions as binding site either for Ca(2+) or anti-calmodulin drugs. Camstatin, a selective peptide blocker of calmodulin, inhibits vanilloid-induced Ca(2+)-uptake in intact TRPV1(+) cells, and suggests an extracellular site of inhibition. TRPV1(+), inflammatory pain-conferring nociceptive neurons from sensory ganglia, were blocked by various anti-psychotic and anti-calmodulin drugs. Among them, calmidazolium, the most effective calmodulin agonist, blocked Ca(2+)-entry by a non-competitive kinetics, affecting the TRPV1 at a different site than the vanilloid binding pocket. Data suggest that various calmodulin antagonists dock to an extracellular site, not found in other Ca(2+)-channels. Calmodulin antagonist-evoked inhibition of TRPV1 and NMDA receptors/Ca(2+)-channels was validated by microiontophoresis of calmidazolium to laminectomised rat monitored with extracellular single unit recordings in vivo. These unexpected findings may explain empirically noted efficacy of clinical pain adjuvant therapy that justify efforts to develop hits into painkillers, selective to sensory Ca(2+)-channels but not affecting motoneurons.

Publication: PLoS ONE 2007 ;2(6)::e545.
Publication Date: 2007
Study Author(s): Oláh, Zoltán;Jósvay, Katalin;Pecze, László;Letoha, Tamás;Babai, Norbert;Budai, Dénes;Otvös, Ferenc;Szalma, Sándor;Vizler, Csaba;
Institution: Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary; Acheuron Hungary Ltd., Szeged, Hungary; Acheuron Pharmaceuticals Inc., San Diego, California, United States of America. [email protected]
Shortcut link to this study:
Ca(2+)-loaded calmodulin normally inhibits multiple Ca(2+)-channels upon dangerous elevation of intracellular Ca(2+) and protects cells from Ca(2+)-cytotoxicity, so blocking of calmodulin should theoretically lead to uncontrolled elevation of intracellular Ca(2+). Paradoxically, classical anti-psychotic, anti-calmodulin drugs were noted here to inhibit Ca(2+)-uptake via the vanilloid inducible Ca(2+)-channel/inflamatory pain receptor 1 (TRPV1), which suggests that calmodulin inhibitors may block pore formation and Ca(2+) entry. Functional assays on TRPV1 expressing cells support direct, dose-dependent inhibition of vanilloid-induced (45)Ca(2+)-uptake at microM concentrations: calmidazolium (broad range) > or = trifluoperazine (narrow range) chlorpromazine/amitriptyline>fluphenazine>W-7 and W-13 (only partially). Most likely a short acidic domain at the pore loop of the channel orifice functions as binding site either for Ca(2+) or anti-calmodulin drugs. Camstatin, a selective peptide blocker of calmodulin, inhibits vanilloid-induced Ca(2+)-uptake in intact TRPV1(+) cells, and suggests an extracellular site of inhibition. TRPV1(+), inflammatory pain-conferring nociceptive neurons from sensory ganglia, were blocked by various anti-psychotic and anti-calmodulin drugs. Among them, calmidazolium, the most effective calmodulin agonist, blocked Ca(2+)-entry by a non-competitive kinetics, affecting the TRPV1 at a different site than the vanilloid binding pocket. Data suggest that various calmodulin antagonists dock to an extracellular site, not found in other Ca(2+)-channels. Calmodulin antagonist-evoked inhibition of TRPV1 and NMDA receptors/Ca(2+)-channels was validated by microiontophoresis of calmidazolium to laminectomised rat monitored with extracellular single unit recordings in vivo. These unexpected findings may explain empirically noted efficacy of clinical pain adjuvant therapy that justify efforts to develop hits into painkillers, selective to sensory Ca(2+)-channels but not affecting motoneurons.
PMID: 17579717

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