Antibodies Bradykinin

Histamine is released from mast cells in antigen-antibody reactions, as in anaphylaxis and allergy, which are the most widely known physiological reactions to histamine. However, these potentially fatal reactions are not caused by histamine alone. Other agents present in mast cells, such as serotonin, acetylcholine, bradykinin (a nonapeptide), and a slow-reacting substance or leukotriene (see chapter 8) also contribute. In the stomach, where histamine induces acid secretion, its release seems to be regulated by the peptide hormone pentagastrin. 

There have been a variety of single alanine point mutations experimentally introduced into both rat and human bradykinin B2 receptors. Several of these have been shown to decrease the affinity of bradykinin to the receptor and have been implicated structurally near the agonist binding site. In contrast, at the time of this manuscript, there have been no mutations reported that adversely affect the ability of any peptide antagonists to bind to the receptor. Furthermore, antibodies raised against the certain extracellular domains of the kinin receptor compete with bradykinin for binding to the receptor but have no inhibitory... 

Garcia-Cardena reported in 1996 that the tyrosine phosphorylation of eNOS in bovine aortic endothelial cells (BAEC) resulted in a decrease in enzyme activity whilst immunoprecipitation of caveolin-1, the predominant isoform in endothelial cells, resulted in co-immunoprecipitation of tyrosine phosphorylated eNOS [17]. Michel et al. (1997) further reported that eNOS, also in BAEC, was co-immunoprecipitaed by caveolin-1 antibodies whilst in rat myocytes eNOS was associated with caveolin-3, the cardiac muscle specific type, confirming that eNOS interaction with caveolin is not tissue specific [18]. Immunofluoresence studies in our group have shown that eNOS associates with caveolin-1 in human umbilical vein endothelial cells (HUVEC), and this interaction is abolished by bradykinin (Wyatt, Pedley Mann, 2001 unpublished data) (Figure 3). 

Haasemann, M., et al. (1991). Anti-idiotypic Antibodies Bearing the Internal Image of a Bradykinin Epitope, J. Immunol. 147 3882-3892. 

The theory behind the inclusion of histamine Hi antagonists in the premedication is obvious but the mode of action of corticosteroids is not completely understood so some beheve its inclusion cannot be explained and justified. Corticosteroids ultimately inhibit kaUikrem, a peptide that lowers blood pressure and liberates bradykinin. Corticosteroids also act in the arachidonic acid cascade to inhibit the production of prostaglandins and leukotrienes, so there does seem to be some rationale for their use. There are some indications that premedication prevents the recurrence of many minor reactions. Some, or even many, of these reactions may not be immune mediated, proceeding instead via a nonspecific and low-level histamine release. In the case of severe inunediate reactions, IgE antibody-mediated explosive histamine release from mast cells may overwhelm the potential effectiveness of premedication. 

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