更新于：2024-11-01

B1 receptor x B2 receptor

更新于：2024-11-01

基本信息

关联

项与 B1 receptor x B2 receptor 相关的药物

Breceptin

靶点

B1 receptor x B2 receptor

作用机制

B1 receptor拮抗剂 [+1]

在研机构

ApopLogic Pharmaceuticals, Inc.

原研机构

ApopLogic Pharmaceuticals, Inc.

在研适应症

去势抵抗性前列腺癌 [+4]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

B-9870

靶点

B1 receptor x B2 receptor

作用机制

B1 receptor拮抗剂 [+1]

在研机构-

原研机构-

在研适应症-

非在研适应症

肿瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

CP-0364

靶点

B1 receptor x B2 receptor

作用机制

B1 receptor拮抗剂 [+1]

在研机构-

原研机构

Cortech, Inc.

在研适应症-

非在研适应症

炎症

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 B1 receptor x B2 receptor 相关的临床结果

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100 项与 B1 receptor x B2 receptor 相关的转化医学

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0 项与 B1 receptor x B2 receptor 相关的专利（医药）

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366

项与 B1 receptor x B2 receptor 相关的文献（医药）

2024-11-01·Pharmacological Research

Tissue Kallikrein supplementation in ischemic phase protects the neurovascular unit and attenuates reperfusion-induced injury in ischemic stroke

Article

作者: Zhang, Qin ; Xu, Tingting ; Wang, Xiaochuan ; Ruan, Hang ; Ran, Xiao

Tissue kallikrein (TK) has emerged as a potential neuroprotective agent in ischemic stroke (IS), yet the optimal timing and mechanisms of TK therapy remain unclear. Here, we established a causal link between lower baseline TK levels and an increased risk of stroke through a retrospective, multicenter cohort study involving 2115 initially non-stroke subjects monitored for 5 years. Sequentially, we observed a notable increase in bradykinin receptor 2 (B2R) levels during the ischemic phase of the IS model, while levels of TK and bradykinin receptor 1 (B1R) remained stable. Intriguingly, both B1R and B2R exhibited a significant elevation 24 h after reperfusion. Further investigations in preclinical models demonstrated that TK supplementation activates the PI3K/AKT signaling pathway via enhanced B2R expression during the ischemic phase, leading to nuclear translocation of Hif-1α. This activation enhances the expression of VEGF and eNOS, thereby fortifying the neurovascular unit. Moreover, it suppresses the activation of the kallikrein-kinin system induced by reperfusion injury, effectively reducing inflammation, ROS production, apoptosis, and endothelial barrier dysfunction. Thus, our findings highlight the significance of TK supplementation during the ischemic phase in attenuating reperfusion-induced injury in IS, providing a mechanistic rationale for determining the optimal timing for TK supplementation therapy.

2024-09-01·Inflammation Research

Kinin B1 receptor and TLR4 interaction in inflammatory response

Article

作者: de Almeida Mendes, Fabio ; Cruz, João Victor Roza ; Pesquero, João Bosco ; Stipursky, Joice ; Batista, Carolina

OBJECTIVEWe aimed to broaden our understanding of a potential interaction between B1R and TLR4, considering earlier studies suggesting that lipopolysaccharide (LPS) may trigger B1R stimulation.METHODSWe assessed the impact of DBK and LPS on the membrane potential of thoracic aortas from C57BL/6, B1R, or TLR4 knockout mice. Additionally, we examined the staining patterns of these receptors in the thoracic aortas of C57BL/6 and in endothelial cells (HBMEC).RESULTSDBK does not affect the resting membrane potential of aortic rings in C57BL/6 mice, but it hyperpolarizes preparations in B₁KO and TLR4KO mice. The hyperpolarization mechanism in B₁KO mice involves B2R, and the TLR4KO response is independent of cytoplasmic calcium influx but relies on potassium channels. Conversely, LPS hyperpolarizes thoracic aorta rings in both C57BL/6 and B₁KO mice, with the response unaffected by a B1R antagonist. Interestingly, the absence of B1R alters the LPS response to potassium channels. These activities are independent of nitric oxide synthase (NOS). While exposure to DBK and LPS does not alter B1R and TLR4 mRNA expression, treatment with these agonists increases B1R staining in endothelial cells of thoracic aortic rings and modifies the staining pattern of B1R and TLR4 in endothelial cells. Proximity ligation assay suggests a interaction between the receptors.CONCLUSIONOur findings provide additional support for a putative connection between B1R and TLR4 signaling. Given the involvement of these receptors and their agonists in inflammation, it suggests that drugs and therapies targeting their effects could be promising therapeutic avenues worth exploring.

2024-01-01·Molecular and Cellular Endocrinology

Kinin B1 receptor modulates glucose homeostasis and physical exercise capacity by altering adrenal catecholamine synthesis and secretion

Article

作者: Batista, Rogério Oliveira ; Estrela, Gabriel Rufino ; Oyama, Lila Missae ; Freitas Lima, Leandro Ceotto ; Bader, Michael ; Arruda, Adriano Cleis ; Casarini, Dulce Elena ; Favaroni Mendes, Lys Angela ; Fernandes Gregnani, Marcos ; Kremer, Jean Lucas ; Araújo, Ronaldo Carvalho ; Ornellas, Fábio Henrique ; Budu, Alexandre ; Lotfi, Claudimara Ferini Pacicco

Our group has shown in several papers that kinin B1 receptor (B1R) is involved in metabolic adaptations, mediating glucose homeostasis and interfering in leptin and insulin signaling. Since catecholamines are involved with metabolism management, we sought to evaluate B1R role in catecholamine synthesis/secretion. Using B1R global knockout mice, we observed increased basal epinephrine content, accompanied by decreased hepatic glycogen content and increased glucosuria. When these mice were challenged with maximal intensity exercise, they showed decreased epinephrine and norepinephrine response, accompanied by disturbed glycemic responses to effort and poor performance. This phenotype was related to alterations in adrenal catecholamine synthesis: increased basal epinephrine concentration and reduced norepinephrine content in response to exercise, as well decreased gene expression and protein content of tyrosine hydroxylase and decreased gene expression of dopamine beta hydroxylase and kinin B2 receptor. We conclude that the global absence of B1R impairs catecholamine synthesis, interfering with glucose metabolism at rest and during maximal exercise.