View source for It:Bradykinin.2nd

==Description==
Bradykinin is an activates pain receptors. Bradykinin induces smooth muscle contraction; activates Ca2+-dependent nitric oxide synthetase. Bradykinin can also increase capillary permeability. Bradykinin is a potent stimulator of nitric oxide formation by vascular endothelium. Bradykinin also stimulates prostacyclin formation.
Bradykinin (BK), a nanopeptide (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg), is the prototype of a family of powerful vasodilatory peptides, the kinins. Although known for a long time only as a pro-inflammatory peptide, BK is now considered an important mediator of the benefits of angiotensin I-converting enzyme inhibitors (ACEi). BK is also an important mediator of a new class of drugs, vasopeptidase inhibitors.

==History==
Bradykinin was discovered by three Brazilian physiologists in 1948 its powerful hypotensive effects in animal preparations. Bradykinin was detected in the blood plasma of animals after the addition of venom of Bothrops jararaca (Brazilian lancehead snake), which was brought by Rosenfeld from the Butantan Institute. This discovery was part of a continuing study on circulatory shock and proteolytic enzymes related to the toxicology of snake bites, started by Rocha e Silva as early as 1939. Bradykinin was to prove a new autopharmacological principle,a substance that is released in the body by a metabolic modification from precursors, which are pharmacologically active."The discovery of bradykinin has led to a new understanding of many physiological and pathological phenomena including circulatory shock induced by venoms and toxins."


==2D structure of bradykinin==
[[Image:bradykinin2D.gif]]

==3D Image of Bradykinin==
<jmol>
<jmolApplet>
<size>400</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
24  0.00  0.00           N+0
ATOM      9  C           0       4.072   0.267  -0.196  0.00  0.00           C+0
ATOM     10  O           0       4.421   0.992   0.712  0.00  0.00           O+0
ATOM     11  C           0       2.666   0.357  -0.732  0.00  0.00           C+0
ATOM     12  N           0       1.927   1.386   0.003  0.00  0.00           N+0
ATOM     13  C           0       0.641   1.643  -0.307  0.00  0.00           C+0
ATOM     14  O           0       0.095   1.022  -1.194  0.00  0.00           O+0
ATOM     15  C           0      -0.120   2.701   0.450  0.00  0.00           C+0
ATOM     16  C           0       0.556   4.074   0.253  0.00  0.00           C+0
ATOM     17  C           0      -0.651   5.043   0.140  0.00  0.00           C+0
ATOM     18  C           0      -1.682   4.168  -0.615  0.00  0.00           C+0
ATOM     19  N           0      -1.487   2.808  -0.079  0.00  0.00           N+0
ATOM     20  C           0      -2.410   1.826  -0.074  0.00  0.00           C+0
ATOM     21  O           0      -2.138   0.741   0.394  0.00  0.00           O+0
ATOM     22  C           0      -3.779   2.076  -0.652  0.00  0.00           C+0
ATOM     23  C           0      -3.661   2.422  -2.151  0.00  0.00           C+0
ATOM     24  C           0      -4.887   1.702  -2.772  0.00  0.00           C+0
ATOM     25  C           0      -4.966   0.419  -1.907  0.00  0.00           C+0
ATOM     26  N           0      -4.596   0.857  -0.549  0.00  0.00           N+0
ATOM     27  C           0      -4.947   0.242   0.598  0.00  0.00           C+0
ATOM     28  O           0      -4.584   0.693   1.664  0.00  0.00           O+0
ATOM     29  C           0      -5.791  -1.006   0.556  0.00  0.00           C+0
ATOM     30  N           0      -5.644  -1.740   1.820  0.00  0.00           N+0
ATOM     31  C           0      -7.259  -0.622   0.357  0.00  0.00           C+0
ATOM     32  C           0      -8.099  -1.890   0.189  0.00  0.00           C+0
ATOM     33  C           0      -9.567  -1.506  -0.010  0.00  0.00           C+0
ATOM     34  N           0     -10.371  -2.720  -0.171  0.00  0.00           N+0
ATOM     35  C           0     -11.729  -2.624  -0.364  0.00  0.00           C+0
ATOM     36  N           0     -12.300  -1.453  -0.405  0.00  0.00           N+0
ATOM     37  N           0     -12.484  -3.763  -0.515  0.00  0.00           N+0
ATOM     38  C           0       6.329  -1.631   1.015  0.00  0.00           C+0
ATOM     39  C           0       5.516  -1.020   2.127  0.00  0.00           C+0
ATOM     40  C           0       4.166  -1.299   2.230  0.00  0.00           C+0
ATOM     41  C           0       3.420  -0.739   3.249  0.00  0.00           C+0
ATOM     42  C           0       4.024   0.101   4.167  0.00  0.00           C+0
ATOM     43  C           0       5.374   0.379   4.064  0.00  0.00           C+0
ATOM     44  C           0       6.121  -0.185   3.047  0.00  0.00           C+0
ATOM     45  C           0       9.888  -0.817  -2.955  0.00  0.00           C+0
ATOM     46  H           0      12.151  -2.096  -0.310  0.00  0.00           H+0
ATOM     47  H           0      11.240  -3.097  -2.160  0.00  0.00           H+0
ATOM     48  H           0      10.286  -3.376  -0.683  0.00  0.00           H+0
ATOM     49  H           0       8.875  -2.693  -2.647  0.00  0.00           H+0
ATOM     50  H           0       8.888  -1.190  -0.143  0.00  0.00           H+0
ATOM     51  H           0       6.647   0.289   0.090  0.00  0.00           H+0
ATOM     52  H           0       4.660  -1.197  -1.450  0.00  0.00           H+0
ATOM     53  H           0       2.697   0.617  -1.790  0.00  0.00           H+0
ATOM     54  H           0       2.169  -0.605  -0.610  0.00  0.00           H+0
ATOM     55  H           0       2.363   1.882   0.713  0.00  0.00           H+0
ATOM     56  H           0      -0.148   2.451   1.510  0.00  0.00           H+0
ATOM     57  H           0       1.175   4.327   1.114  0.00  0.00           H+0
ATOM     58  H           0       1.147   4.086  -0.664  0.00  0.00           H+0
ATOM     59  H           0      -1.022   5.321   1.126  0.00  0.00           H+0
ATOM     60  H           0      -0.389   5.927  -0.441  0.00  0.00           H+0
ATOM     61  H           0      -2.695   4.514  -0.410  0.00  0.00           H+0
ATOM     62  H           0      -1.483   4.185  -1.686  0.00  0.00           H+0
ATOM     63  H           0      -4.263   2.895  -0.119  0.00  0.00           H+0
ATOM     64  H           0      -3.728   3.499  -2.305  0.00  0.00           H+0
ATOM     65  H           0      -2.733   2.029  -2.566  0.00  0.00           H+0
ATOM     66  H           0      -5.790   2.303  -2.662  0.00  0.00           H+0
ATOM     67  H           0      -4.708   1.457  -3.819  0.00  0.00           H+0
ATOM     68  H           0      -5.980   0.019  -1.913  0.00  0.00           H+0
ATOM     69  H           0      -4.260  -0.327  -2.271  0.00  0.00           H+0
ATOM     70  H           0      -5.465  -1.637  -0.271  0.00  0.00           H+0
ATOM     71  H           0      -5.955  -1.120   2.553  0.00  0.00           H+0
ATOM     72  H           0      -6.300  -2.505   1.789  0.00  0.00           H+0
ATOM     73  H           0      -7.610  -0.066   1.226  0.00  0.00           H+0
ATOM     74  H           0      -7.354  -0.002  -0.535  0.00  0.00           H+0
ATOM     75  H           0      -7.748  -2.446  -0.680  0.00  0.00           H+0
ATOM     76  H           0      -8.003  -2.509   1.080  0.00  0.00           H+0
ATOM     77  H           0      -9.918  -0.949   0.859  0.00  0.00           H+0
ATOM     78  H           0      -9.662  -0.886  -0.902  0.00  0.00           H+0
ATOM     79  H           0      -9.946  -3.591  -0.140  0.00  0.00           H+0
ATOM     80  H           0     -13.258  -1.385  -0.541  0.00  0.00           H+0
ATOM     81  H           0     -12.059  -4.634  -0.485  0.00  0.00           H+0
ATOM     82  H           0     -13.442  -3.695  -0.651  0.00  0.00           H+0
ATOM     83  H           0       5.905  -2.598   0.744  0.00  0.00           H+0
ATOM     84  H           0       7.358  -1.766   1.349  0.00  0.00           H+0
ATOM     85  H           0       3.694  -1.955   1.513  0.00  0.00           H+0
ATOM     86  H           0       2.365  -0.956   3.329  0.00  0.00           H+0
ATOM     87  H           0       3.441   0.539   4.963  0.00  0.00           H+0
ATOM     88  H           0       5.846   1.035   4.781  0.00  0.00           H+0
ATOM     89  H           0       7.176   0.033   2.967  0.00  0.00           H+0
ATOM     90  H           0      10.429  -0.081  -2.359  0.00  0.00           H+0
ATOM     91  H           0      10.547  -1.214  -3.727  0.00  0.00           H+0
ATOM     92  H           0       9.026  -0.343  -3.423  0.00  0.00           H+0
CONECT    1    2   46    0    0                                         NONE  98
CONECT    2    1    3   47   48                                         NONE  99
CONECT    3    2    4   45   49                                         NONE 100
CONECT    4    3    5   50    0                                         NONE 101
CONECT    5    4    6    7    0                                         NONE 102
CONECT    6    5    0    0    0                                         NONE 103
CONECT    7    5    8   38   51                                         NONE 104
CONECT    8    7    9   52    0                                         NONE 105
CONECT    9    8   10   11    0                                         NONE 106
CONECT   10    9    0    0    0                                         NONE 107
CONECT   11    9   12   53   54                                         NONE 108
CONECT   12   11   13   55    0                                         NONE 109
CONECT   13   12   14   15    0                                         NONE 110
CONECT   14   13    0    0    0                                         NONE 111
CONECT   15   13   19   16   56                                         NONE 112
CONECT   16   15   17   57   58                                         NONE 113
CONECT   17   16   18   59   60                                         NONE 114
CONECT   18   17   19   61   62                                         NONE 115
CONECT   19   18   15   20    0                                         NONE 116
CONECT   20   19   21   22    0                                         NONE 117
CONECT   21   20    0    0    0                                         NONE 118
CONECT   22   20   26   23   63                                         NONE 119
CONECT   23   22   24   64   65                                         NONE 120
CONECT   24   23   25   66   67                                         NONE 121
CONECT   25   24   26   68   69                                         NONE 122
CONECT   26   25   22   27    0                                         NONE 123
CONECT   27   26   28   29    0                                         NONE 124
CONECT   28   27    0    0    0                                         NONE 125
CONECT   29   27   30   31   70                                         NONE 126
CONECT   30   29   71   72    0                                         NONE 127
CONECT   31   29   32   73   74                                         NONE 128
CONECT   32   31   33   75   76                                         NONE 129
CONECT   33   32   34   77   78                                         NONE 130
CONECT   34   33   35   79    0                                         NONE 131
CONECT   35   34   36   37    0                                         NONE 132
CONECT   36   35   80    0    0                                         NONE 133
CONECT   37   35   81   82    0                                         NONE 134
CONECT   38    7   39   83   84                                         NONE 135
CONECT   39   38   44   40    0                                         NONE 136
CONECT   40   39   41   85    0                                         NONE 137
CONECT   41   40   42   86    0                                         NONE 138
CONECT   42   41   43   87    0                                         NONE 139
CONECT   43   42   44   88    0                                         NONE 140
CONECT   44   43   39   89    0 
M  END</inlineContents>
</jmolApplet>
</jmol>

==Snake-like view of Bradykinin==
[[Image:Snake-like.gif]]

==Physiological role==
Bradykinin is a potent endothelium-dependent vasodilator, causes contraction of non-vascular smooth muscle, increases vascular permeability and also is involved in the mechanism of pain. In some aspects, it has similar actions to that of histamine, and like histamine is released from venules rather than arterioles.

Bradykinin raises internal calcium levels in neocortical astrocytes causing them to release glutamate.

Bradykinin is also thought to be the cause of the dry cough in some patients on angiotensin converting enzyme (ACE) inhibitor drugs. This refractory cough is a common cause for stopping ACE-inhibitor therapy.



==Reaction Mechanism==
[[Image:leukotrienesynthesis.gif]]
[[Image:prostaglandinsynthesis.gif]]
[[Image:Brady.gif]]

==Role of bradykinin in preconditioning and protection of the ischaemic myocardium==
[[Image:role.gif]]
[[Image:role1.gif]]
[[Image:role3.gif]]
[[Image:role4.gif]]

==Further Reading==
*[History and a review of the kinin system
http://www.jstor.org/view/00804649/ap000191/00a00110/0]
*[Bradykinin attenuates glucagon-inducedleucine oxidation in humans
http://ajpendo.physiology.org/cgi/reprint/259/2/E239.pdf]
==External Links==
*[Use of peptidic bradykinin antagonists for the treatment and prevention of Alzheimer's disease
http://www.patentstorm.us/patents/6245736-description.html]
*[Role of bradykinin in preconditioning and protection of the ischaemic myocardium
http://www.nature.com/bjp/journal/v135/n4/full/0704548a.html;jsessionid=FC42D95BDDC87938C5411B0E85323C66]
*[Mechanisms of ACE Inhibitor Angioedema 
http://www.clinimmsoc.org/meetings/summerschool06/presentations/banerji_aleena.pdf]