Introduction of BDKRB2

BDKRB2 (also called B2 receptor) is a constitutively expressed bradykinin receptor which mediates the majority of the vascular and metabolic actions of kinins. These B2 receptors are ubiquitously expressed by different cell types, such as vascular endothelial and smooth muscle cells, nonvascular smooth muscle cells of the uterus and intestine, fibroblasts, epithelial cells, various tumor cells, and also on leukocytes and in the central nervous system. The B2 receptors are G protein-coupled, 7-transmembrane-spanning receptors. They signal mainly through Gα_q, which stimulates phospholipase C to increase intracellular free calcium.

Functions of BDKRB2 Membrane Protein

B2R activated by its endogenous ligand bradykinin participates in various physiological processes including neurogenesis, neuronal differentiation, neuroprotection, and control of inflammation and blood pressure. Studies with B2 receptor knockout mice have shown that the animals develop normally. However, one study found that when animals are fed a high-salt diet, severe hypertension occurs. It has also been reported that the renin-angiotensin system was abnormal (the kallikrein-kinin system and the renin-angiotensin system are antagonistic hemodynamic regulatory systems that play important roles in blood pressure homeostasis) and abnormal renal development occurred. A variety of cardiac defects have also been reported as well as chronically elevated heart rate. A single-nucleotide polymorphism of the BDKRB2 gene promoter, C allele, has been demonstrated to be an independent risk factor for essential hypertension in several ethnic groups. Moreover, several other alleles have been reported and were found to be differentially associated with several disease states.

Fig.1 Human BDKRB2. (Joedicke, 2018)

Applications of BDKRB2 Membrane Protein in Literature

1. Ji B., et al. Neuroprotection of bradykinin/bradykinin B2 receptor system in cerebral ischemia. Biomedicine & Pharmacotherapy. 2017, 94: 1057-1063. PMID: 28810528

This article reported the mechanisms of BK/B2R-mediated neuroprotective effects in the peripheral and central nervous systems.

2. Caetano A L., et al. Kinin B2 receptor can play a neuroprotective role in Alzheimer's disease. Neuropeptides. 2015, 53: 51-62. PMID: 26387425

This study evaluated the participation of B1R and B2R in Aβ peptide-induced cognitive deficits through the evaluation of densities of kinin receptors, synapses, cell bodies and number of Aβ deposits in the brain of three Alzheimer’s disease (AD) models. Study data suggested that B2R displayed a neuroprotective effect and can be regarded as a potential therapeutic target in AD.

3. Luo K., et al. The Risk of bradykinin B2 receptor-58T/C gene polymorphism on hypertension: A meta‐analysis. International Journal of Clinical & Experimental Medicine. 2015, 8(11): 19917-27. PMID: 26884904

This study did a meta-analysis to analyze the relationship between the risk of hypertension and BDKRB2-58T/C gene polymorphism. The results suggested that -58C allele and -58CC genotype increased the risk of hypertension.

4. Rodi D., et al. Bradykinin B 2, receptors increase hippocampal excitability and susceptibility to seizures in mice. Neuroscience. 2013, 248(38): 392-402. PMID: 23811399

This study used two different models to investigate the susceptibility to seizures of B1 knockout (KO) and B2 KO mice. The results showed that B2 receptors might have a role in the responsiveness to epileptogenic insults and/or in the early period of epileptogenesis.

BDKRB2 Preparation Options

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Reference

1. Joedicke, L., et al. (2018). The molecular basis of subtype selectivity of human kinin g-protein-coupled receptors. Nature Chemical Biology. 14(3), 284-290.

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