Kinin B1 receptors: a review

doi:10.1016/0162-3109(95)00011-H

Immunopharmacology

Volume 30, Issue 1, June 1995, Pages 1-26

Immunopharmacology

https://doi.org/10.1016/0162-3109(95)00011-H Get rights and content

Abstract

The kinin B₁ receptor has been initially defined as the one mediating the contractile effect of bradykinin (BK)-related peptides in the isolated rabbit aorta. The B₁ receptor is selectively sensitive to kinin metabolites without the C-terminal arginine residue, e.g. des-Arg⁹-BK and Lys-des-Arg⁹-BK; it is apparently rapidly up-regulated in immunopathology under the influence of cytokines and is further regulated by growth factors. Progress in the understanding of this pharmacologic entity is reviewed, including the development of B₁ receptor agonists and antagonists, binding assays, physiopathological applications and the recent cloning and sequencing of the receptor cDNA.

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Cited by (361)

The role of kallikrein-kinin and renin-angiotensin systems in COVID-19 infection
2021, Peptides
Citation Excerpt :
Once formed, Lys-Bk can still be converted to BK by the action of an aminopeptidase. Other carboxypeptidases (M and N) remove arginine from the C-terminal and give rise to desArg9-BK (DABK) and Lys-desArg9-BK (LDABK), respectively from BK and Lys-BK [74,75]. The interconnection of the kallikrein-kinin and renin-angiotensin systems is done by angiotensin-converting enzymes present in both systems.
In November 2019 the first cases of a novel acute respiratory syndrome has been reported in Wuhan province, China. Soon after, in January 2020 the World Health Organization declared a pandemic state due to the dissemination of a virus named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of coronavirus disease 2019 (COVID-19). Being an unknown disease, it is essential to assess not only its main characteristic features and overall clinical symptomatology but also its patient infection mode and propagation to design appropriate clinical interventions and treatments. In this review the pathophysiology of SARS-CoV-2 infection and how the virus enters the cells and activates the immune system are described. The role of three systems involved in the SARS- CoV-2 infection (renin-angiotensin, kinin and coagulation systems) is discussed with the objectives to identify and try to explain several of the events observed during the evolution of the disease and to suggest possible targets for therapeutic interventions.
Kinin B1 receptor: A target for neuroinflammation in hypertension
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Citation Excerpt :
Physiological effects of kinins are mediated by highly selective, G-protein coupled receptors with seven transmembrane domains, an extracellular amino terminal and an intracellular carboxy terminal domain, namely B1 (B1R, BDKRB1) and B2 (B2R, BDKRB2). BK and KD are relatively selective ligands for the B2R, whereas DABK and DAKD are selective ligands for the B1R [4,5]. The constitutively expressed B2R is widely distributed and mediates most of the biological actions of BK.
Kinins are a family of oligopeptides of the kallikrein-kinin system that act as potent vasoactive hormones and inflammatory mediators. The bioactive kinins mainly consist of bradykinin and kallidin, and their metabolites des-Arg⁹-bradykinin and des-Arg¹⁰-kallidin. Physiological effects of kinins are mediated by activation of highly selective G-protein coupled kinin B1 and B2 receptors. Growing evidence suggests that B1 receptor activation mediates diverse physiological and pathological features of cardiovascular diseases. However, studies are limited regarding the impact of B1 receptor mediated neuroinflammation on the development of hypertension and other cardiovascular diseases. Given the potential role for B1 receptor activation in immune cell infiltration, microglia activation, and cytokine production within the central nervous system, B1 receptor mediated signaling cascades might result in elevated neuroinflammation. In this review, we will discuss the potential pro-inflammatory role of B1 receptor activation in hypertension. A better understanding of B1 receptor inflammatory signaling may lead to the development of therapeutics that target B1 receptors to treat neurogenic hypertension.
New insights into the stereochemical requirements of the bradykinin B1 receptor antagonists binding
2016, Journal of Molecular Graphics and Modelling
Bradykinin (BK) is a nonapeptide involved in several pathophysiological conditions including among others, septic and haemorrhagic shock, anaphylaxis, arthritis, rhinitis, asthma, inflammatory bowel disease. Accordingly, BK antagonists have long been sought after for therapeutic intervention. Action of BK is mediated through two different G-protein coupled receptors known as B1 and B2. Although there are several B1 antagonists reported in literature, their pharmacological profile is not yet optimal so that new molecules need to be discovered. In the present work we have constructed an atomistic model of the B1 receptor and docked diverse available non-peptide antagonists in order to get a deeper insight into the structure-activity relationships involving binding to this receptor. The model was constructed by homology modeling using the chemokine CXC4 and bovine rhodopsin receptors as template. The model was further refined using molecular dynamics for 600 ns with the protein embedded in a POPC bilayer. From the refinement process we obtained an average structure that was used for docking studies using the Glide software. Antagonists selected for the docking studies include Compound 11, Compound 12, Chroman28, SSR240612, NPV-SAA164 and PS020990. The results of the docking study underline the role of specific receptor residues in ligand binding. The results of this study permitted to define a pharmacophore that describes the stereochemical requirements of antagonist binding, and can be used for the discovery of new compounds.
Differential regulation of astrocyte prostaglandin response by kinins: Possible role for mitogen activated protein kinases
2014, European Journal of Pharmacology
The role of kinins, well known as peripheral inflammatory mediators, in the modulation of brain inflammation is not completely understood. The present data show that bradykinin, a B₂ receptor agonist, enhanced both basal and lipopolysaccharide (LPS)-induced cyclooxygenase-2 mRNA and protein levels and prostaglandin E₂ synthesis in primary rat astrocytes. By contrast, Lys-des-Arg⁹-bradykinin, which is a bradykinin breakdown product and a selective kinin B₁ receptor agonist, attenuated both basal and LPS-induced astrocyte cyclooxygenase-2 mRNA levels and prostaglandin E₂ production. Pre-treating the cells with p42/p44 MAPK but not with JNK or p38 inhibitors completely abrogated PGE₂ synthesis in cells stimulated with LPS in the presence of bradykinin or bradykinin B₁ receptor agonist. Bradykinin, but not the bradykinin B₁ receptor agonist, augmented p42/p44 MAPK phosphorylation. The phosphorylation of JNK and p38 was not altered upon exposure to Bradykinin or the bradykinin B₁ receptor agonist. These results suggest that the dual delayed effect of kinins on PGE₂ synthesis may be due to differential regulation of COX-2 and signaling molecules such as p42/p44 MAPKs. Thus, kinins may exert opposing actions on brain inflammation and neurodegenerative diseases.
Preclinical pharmacology, metabolic stability, pharmacokinetics and toxicology of the peptidic kinin B1 receptor antagonist R-954
2014, Peptides
We previously showed that R-954 (AcOrn[Oic²,(αMe)Phe⁵,dβNal⁷,Ile⁸]desArg⁹-bradykinin) is a potent, selective and stable peptide antagonist of the inducible GPCR kinin B1 receptor. This compound shows potential applications for the treatment of several diseases, including cancer and neurological disturbances of diabetes. To enable clinical translation, more information regarding its pharmacological, pharmacokinetics (PK) and toxicological properties at preclinical stage is warranted. This was the principal objective of the present study. Herein, specificity of R-954 was characterized in binding studies on 133 human molecular targets to reveal minor cross-reactivities against the angiotensin AT₂ and the bombesin receptors (110- and 330-fold lower affinity than for B1R, respectively). The pharmacokinetic of R-954 was studied in both normal and streptozotocin-diabetic anaesthetized rats providing half-lives of 1.9–2.7 h. R-954 does not appear to be metabolized in the rat circulation and in several rat tissue homogenates, as the kidney, lung and liver. It appears to be excreted as parent drug in the bile (21%) and in urine. A preliminary toxicological profile of R-954 was obtained in rats under various administration routes. R-954 appears to be well tolerated. Overall, these results indicate that R-954 exhibits favorable preclinical pharmacological/PK characteristics and encouraging safety profiles, suitable for early studies in humans.
Renal, cardiac, neurological, cutaneous and coagulopathic long-term manifestations of COVID-19 after recovery; A review
2022, Epidemiology and Infection

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Review articleKinin B1 receptors: a review

Abstract

Peptides

Eur J Pharmacol.

Eur J Pharmacol

Regul Peptides

Life Sci.

Life Sci

Eur J Pharmacol

Neuropharmacology

Eur J Pharmacol

Immunopharmacology

Eur J Pharmacol

Peptides

J Biol Chem

J Neuroimmunol

J Biol Chem

Biochem Pharmacol

Pharmacol Ther

Biochim Biophys Acta

Biochem Biophys Res Comm

J Biol Chem

Neuropeptides

Neuropeptides

Immunopharmacology

Gen Pharmacol

Life Sci

J Biol Chem

Eur J Pharmacol

Eur J Pharmacol

Biochem Pharmacol

Central bradykininergic system in normotensive and hypertensive rats

Clin Sci

Synergistic effect of recombinant human epidermal growth factor and des-Arg9-bradykinin, on rat croton oil-induced granulation tissue contraction

Br J Pharmacol

Binding of [3H]des-Arg9-BK to rabbit anterior mesenteric vein

Can J Physiol Pharmacol

Evidence for the activation of the kallikrein-kinin system in experimental asbestosis

Res Comm Chem Pathol Pharmacol

Bradykinin and respiratory membranes

Am Rev Resp Dis

Evidence for existence of two distinct bradykinin receptors on rat mesangial cells

Am J Physiol

Bradykinin antagonists

Annu Rev Pharmacol Toxicol

Further evidence for the existence of two receptor sites for bradykinin responsible for the diphasic effect in the rat isolated duodenum

Br J Pharmacol

Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo

Br J Pharmacol

A bradykinin antagonist inhibits carrageenan edema in rats

Naunyn Schmiedeberg's Arch Pharmacol

New, potent, selective radioligands for studying bradykinin B1 and B2 receptors

Bradykinin B1 receptors in the rabbit urinary bladder: induction of responses, smooth muscle contraction, and phosphatidylinositol hydrolysis

Br J Pharmacol

Effect of des-arginine9-bradykinin and other bradykinin fragments on the synthesis of prostacyclin and the binding of bradykinin by vascular cells in culture

Agents Actions

Effect of protein kinase C and calcium on bradykinin-mediated contractions of rabbit vessels

Hypertension

An arginine carboxypeptidase generated during coagulation is diminished or absent in patients with rheumatoid arthritis

J Lab Clin Invest

Mechanisms involved in the contractile responses of kinins in rat portal vein rings: mediation by B1 and B2 receptors

J Pharmacol Exp Ther

Protective effects of BK on the ischemic heart: implication of the B1 receptor

Br J Pharmacol

Design, synthesis, and in vitro activity of bis(succinimido)hexane peptide heterodimers with combined B1 and B2 antagonist activity

J Med Chem

Pharmacology of nasal provocation with bradykinin: studies of tachyphylaxis, cyclooxygenase inhibition, alpha-adrenergic stimulation, and receptor subtype

Int Arch Allergy Appl Immunol

Conversion of B1 kinin receptor-mediated vascular relaxation to contraction

Hypertension

Interleukin-1 gene expression in rabbit vascular tissue in vivo

Am J Pathol

Review article
Kinin B₁ receptors: a review

Synergistic effect of recombinant human epidermal growth factor and des-Arg⁹-bradykinin, on rat croton oil-induced granulation tissue contraction

Binding of [³H]des-Arg⁹-BK to rabbit anterior mesenteric vein

Studies on the induction of pharmacological responses to des-Arg⁹-bradykinin in vitro and in vivo

New, potent, selective radioligands for studying bradykinin B₁ and B₂ receptors

Bradykinin B₁ receptors in the rabbit urinary bladder: induction of responses, smooth muscle contraction, and phosphatidylinositol hydrolysis

Effect of des-arginine⁹-bradykinin and other bradykinin fragments on the synthesis of prostacyclin and the binding of bradykinin by vascular cells in culture

Mechanisms involved in the contractile responses of kinins in rat portal vein rings: mediation by B₁ and B₂ receptors

Protective effects of BK on the ischemic heart: implication of the B₁ receptor

Design, synthesis, and in vitro activity of bis(succinimido)hexane peptide heterodimers with combined B₁ and B₂ antagonist activity

Conversion of B₁ kinin receptor-mediated vascular relaxation to contraction