Introduction of BDKRB1

Bradykinin is a nine-amino-acid peptide generated by kallikrein cleavage of kininogen precursor proteins in tissue and plasma. Two bradykinin receptors have been identified as mediators of bradykinin signaling: BDKRB1 and BDKRB2. These are cell surface, G-protein coupled receptors of the seven-transmembrane domain family. The human BDKRB1 receptor has a predicted sequence of 353 amino acids and is only 36% homologous to BDKRB2 receptors. The expression of BDKRB1 is induced during trauma, injury, and inflammation. It is best characterized as signaling via coupling to Gq alpha subunits (particularly Gq/11), leading to activation of phospholipase C beta, hydrolysis of PI, and an intracellular increase in free calcium. The BDKRB1 receptor is an inducible receptor, which can be rapidly upregulated in biological systems following some types of tissue injury. The expression of this receptor is reported to be induced by a variety of cytokines.

Functions of BDKRB1 Membrane Protein

Studies have reported that B1 receptors have been implicated in hyperalgesia, plasma extravasation, white blood cell activation and accumulation, and in the control of blood pressure. B1 receptor knockout mice have been reported to develop normally and to have normal blood pressure. However, when inflammatory stimuli are applied, dramatic reductions in accumulation and apoptosis of neutrophils have been reported, as well as hypoalgesia. Moreover, in other studies, the BDKRB1 receptor was reported to play a crucial role in hyperglycemia and renal abnormalities as well as in altered vascular permeability associated with type 1 diabetes. It was also involved in the development of hyperalgesia measured in streptozotocin (STZ)-induced type 1 diabetes of murine models. Both acute and chronic administration of the selective B1R antagonist R-715 and R-954 significantly inhibited the hyperalgesic activity.

Fig.1 Human BDKRB1. (Joedicke, 2018)

Applications of BDKRB1 Membrane Protein in Literature

1. Bitencourt R M., et al. Blockade of hippocampal bradykinin B1 receptors improves spatial learning and memory deficits in middle-aged rats. Behavioural brain research. 2017, 316: 74-81. PMID: 27566183

This study investigated the role of hippocampal bradykinin receptors B1R and B2R on the cognitive decline of middle-aged rats. Selective B1R antagonists, especially orally active non-peptide antagonists, may represent drugs of potential interest to counteract the age-related cognitive decline.

2. Amouroux G., et al. Synthesis and evaluation of a ⁶⁸Ga-labeled bradykinin B1 receptor agonist for imaging with positron emission tomography. Bioorg Med Chem. 2016, 25(2): 690-696. PMID: 27908753

This article reported the synthesis and evaluation of a novel ⁶⁸Ga-labeled bradykinin B1 receptor agonist, ⁶⁸Ga-Z01115. It was suggested that this agonist was a promising tracer for imaging the expression of B1 receptor that was overexpressed in a variety of cancers.

3. Kahn R., et al. Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis. Kidney International. 2017, 91(1): 96-105. PMID: 27914700

This study investigated whether leukocyte-derived microvesicles bear B1-kinin receptors during vasculitis and if microvesicles transferred functional B1-receptors to recipient cells, thus promoting inflammation.

4. Lin K S., et al. In vivo radioimaging of bradykinin receptor B1, a widely overexpressed molecule in human cancer. Cancer Research. 2015, 75(2): 387-93. PMID: 25488751

This article evaluated the feasibility of using radiolabeled kallidin derivatives to visualize B1R expression in a preclinical model of B1R-positive tumors. The results presented noninvasive B1R detection by PET imaging as a general tool to visualize many human cancers.

5. Naidu N., et al. B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration. African Health Sciences. 2014, 14(3): 657-62. PMID: 25352885

This study investigated the effect of two bradykinin receptor (B1R and B2R) agonists on growth and motility of prostate tumor (DU145) and microvascular endothelial cells (dMVECs). The study results showed that bradykinin receptors were promising therapeutic targets in the development of alternative approaches to cancer therapy.

BDKRB1 Preparation Options

Solubilization and stabilization of membrane proteins are key to facilitate their functional and structural research of this class of delicate and fascinating proteins as well as drug discovery applications. Creative Biolabs has acquired useful experience and skills to successfully reconstitute difficult-to-prepare membrane proteins into functional formats. We provide various membrane mimetic systems to reconstitute your membrane protein of interest. Each of the systems has both advantages and limitations for a specific target protein and should be determined based on the information and research purpose you pursue. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-BDKRB1 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

Creative Biolabs has accomplished a number of difficult projects and our seasoned scientists will certainly help you with the optimal choice. contact us to experience the great value of our excellent services.

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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