B2 bradykinin receptors

Bas M. Bier H. Greve J, Kojda G, Hoffmann T Novel pharmacotherapy of acute hereditary angioedema with bradykinin B2-receptor antagonist icatibant. Allergy 2006 61 1490-1492. 

Contribution of bradykinin B2 receptor dysfunction to abnormal coronary vaso-motion in humans. J Am Coll Cardiol 2000 36 1467-1473. 

Pizard, A., Marchetti, J., Allegrini, J., Alhenc-Gelas, F., and Rajerison, R. M. (1998) Negative cooperativity in the human bradykinin B2 receptor. J. Biol. Chem. 273, 1309-1315. 

Sawada Y, Kayakiri H, Abe Y, et al. A new class of nonpeptide bradykinin B2 receptor ligands, incorporating a 4-aminoquinoline framework. Identification of a key pharmacophore to determine species difference and agonist/antagonist profile. 7 Med Chem 2004 47 2667-77. 

The AT2 receptor has a structure and affinity for Ang II similar to those of the A receptor. In contrast, however, stimulation of AT2 receptors causes vasodilation that may serve to counteract the vasoconstriction resulting from ATi receptor stimulation. AT2 receptor-mediated vasodilation appears to be nitric oxide (NO)-dependent and may involve the bradykinin B2 receptor-NO-cGMP pathway. 

Nearly all cells express kinin receptors that mediate the activities of both bradykinin and kallidin. The activation of these G-protein coupled receptors causes relaxation of venular smooth muscle and hypotension, increased vascular permeability, contraction of smooth muscle of the gut and airway leading to increased airway resistance, stimulation of sensory neurons, alteration of ion secretion of epithelial cells, production of nitric oxide, release of cytokines from leukocytes, and the production of eicosanoids from various cell types [11,12]. Because of this broad spectrum of activity, kinins have been implicated as an important mediator in many pathophysiologies including pain, sepsis, asthma, rheumatoid arthritis, pancreatitis, and a wide variety of other inflammatory diseases. Moreover, a recent report demonstrated that bradykinin B2 receptors on the surface of human fibroblasts were upregulated three-fold beyond normal in patients with Alzheimer s disease, implicating bradykinin as a participant in the peripheral inflammatory processes associated with that disease [13]. 

One noteworthy observation was that NPC 18325 showed divergent behavior when evaluated against different species homologues of the bradykinin B2 receptor. Notably, in the guinea pig ileal membrane preparation assay, the affinity for the receptor was approximately 10-fold less than what had been... 

Table 3 Sequences of Pfieudopeplides and Their Bradykinin B2 Receptor Affinities...

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... 

Not surprisingly, compound I showed divergent potency when assayed in different species homologues of the bradykinin B2 receptor. In particular, in a model of bradykinin-induced hypotension in rats and rabbits, it showed no activity. Likewise, it did not block bradykinin-induced contraction of the isolated guinea pig ileum. Since compound I is considerably smaller than previously reported decapeptide antagonists, subtle structural differences (which are... 

Xi L, Das A, Zhao ZQ, Merino VF, Bader M, Kukreja RC (2008) Loss of myocardial ischemic postconditioning in adenosine A( and bradykinin B2 receptors gene knockout mice. Circulation 118(14 Suppl) S32-S37... 

Soskic, V., Nyakatura, E., Roos, M., Muller-Esterl, W., and Godovac-Zimmermann, J. (1999) Correlations in palmitoylation and multiple phosphorylation of rat bradykinin B2 receptor in Chinese hamster ovary cells. J. Biol. Chem. 26, 8539-8545. 

In rats, ramipril reduced renal lithium clearance and increased fractional lithium reabsorption in association with decreased systolic blood pressure and decreased sodium excretion. These effects were attenuated by icati-bant, a specific bradykinin B2 receptor antagonist (577). 

Hellal F, Pruneau D, Palmier B, Faye P, Croci N, Plotkine M, Marchand-Verrecchia C (2003) Detrimental role of bradykinin B2 receptor in a murine model of diffuse brain injury. J Neurotrauma 20 841-851... 

Ivashkova Y, Svetnitsky A, Mayzler O, Pruneau D, Benifla M, Fuxman Y, Cohen A, Artru AA, Shapira Y (2006) Bradykinin B2 receptor antagonism with LF 18-1505T reduces brain edema and improves neurological outcome after closed head trauma in rats. J Trauma 61 879-885... 

Lorenzl S, Kodel U, Frei K, Pfister HW (1996) Effect of the bradykinin B2 receptor antagonist Hoel40 in experimental pneumococcal meningitis in the rat. Eur J Pharmacol 308 335-341 Lumenta DB, Plesnila N, Klasner B, Baethmann A, Pruneau D, Schmid-Elsaesser R, Zausinger S (2006) Neuroprotective effects of a postischemic treatment with a bradykinin B2 receptor antagonist in a rat model of temporary focal cerebral ischemia. Brain Res 1069 227-234 Mac Donald CL, Dikranian K, Bayly P, Holtzman D, Brody D (2(X)7) Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J Neurosci 27 11869-11876... 

Dose-relation collateral effect Time-course time-independent Susceptibility factors genetic (polymorphisms of the bradykinin B2 receptor gene and the ACE gene) sex... 

It was concluded that 1) bradykinin has a biphasic effect on afferent arterioles 2) both dilation and constriction may be mediated by bradykinin B2 receptors and 3) the mechanisms of vasodilation and vasoconsbiction are due to cyclooxygenase products, not nitric oxide. 

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