Regulation by Interleukin-1β of Gene Expression of Bradykinin B1 Receptor in MH-S Murine Alveolar Macrophage Cell Line

Tsukagoshi, Hideo; Shimizu, Yūji; Horie, Takeo; Fukabori, Yoshitatsu; Shimizu, Yasuo; Iwamae, Shigenori; Hisada, Takeshi; Ishizuka, Tamotsu; Iizuka, Kunihiko; Dobashi, Kunio; Mori, Masataka

doi:10.1006/bbrc.1999.0798

Cited by 20 publications

(12 citation statements)

References 30 publications

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“…Thus, it is likely that the high dose of 10 mg/kg ELN441958 s.c. reduces early carrageenan-induced hyperalgesia by mechanisms other than prostanoid production. Because B 1 agonists promote generation of NO (Sangsree et al, 2003), cytokine release (Tsukagoshi et al, 1999), and neutrophil infiltration (Ehrenfeld et al, 2006), B 1 antagonists may reduce the hyperalgesia elicited by these proinflammatory factors.…”

Section: Downloaded Frommentioning

confidence: 99%

Pharmacological, Pharmacokinetic, and Primate Analgesic Efficacy Profile of the Novel Bradykinin B₁ Receptor Antagonist ELN441958

Hawkinson

Szőke²,

Garofalo³

et al. 2007

J Pharmacol Exp Ther

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The bradykinin B 1 receptor plays a critical role in chronic pain and inflammation, although efforts to demonstrate efficacy of receptor antagonists have been hampered by species-dependent potency differences, metabolic instability, and low oral exposure of current agents. The pharmacology, pharmacokinetics, and analgesic efficacy of the novel benzamide B 1 receptor antagonist 7-chloro-2-[3-(9-pyridin-4-yl-3,9-diazaspiro [5.5] receptors with a rank order potency (K B , nanomolar) of human (0.12 Ϯ 0.02) ϳ rhesus monkey (0.24 Ϯ 0.01) Ͼ rat (1.5 Ϯ 0.4) Ͼ mouse (14 Ϯ 4). ELN441958 had good permeability and metabolic stability in vitro consistent with high oral exposure and moderate plasma half-lives in rats and rhesus monkeys. Because ELN441958 is up to 120-fold more potent at primate than at rodent B 1 receptors, it was evaluated in a primate pain model. ELN441958 dose-dependently reduced carrageenaninduced thermal hyperalgesia in a rhesus monkey tail-withdrawal model, with an ED 50 ϳ3 mg/kg s.c. Naltrexone had no effect on the antihyperalgesia produced by ELN441958, indicating a lack of involvement of opioid receptors. ELN441958 is a novel small molecule bradykinin B 1 receptor antagonist exhibiting high oral bioavailability and potent systemic efficacy in rhesus monkey inflammatory pain.Antagonism of bradykinin receptors may prove to be a viable therapeutic strategy to reduce pain and inflammation. Initial interest focused on the constitutively expressed bradykinin B 2 receptor, which is selectively activated with high affinity by bradykinin (BK) and kallidin (KD). Recently, there has been considerable interest in the inducible B 1 receptor, which is selectively activated by desArg 9 -bradykinin (DABK) and desArg 10 -kallidin (DAKD), the N-terminal arginine-cleaved metabolites of BK and KD (Leeb-Lundberg et al., 2005

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Section: Downloaded Frommentioning

confidence: 99%

Pharmacological, Pharmacokinetic, and Primate Analgesic Efficacy Profile of the Novel Bradykinin B₁ Receptor Antagonist ELN441958

Hawkinson

Szőke²,

Garofalo³

et al. 2007

J Pharmacol Exp Ther

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“…To date, constitutive B 1 receptor expression has been documented in vascular tissues of dogs ( Belichard et al ., 1996 ; Staszewska‐Woolley & Woodman, 1991 ), the central nervous system of spontaneously hypertensive rats ( Emanueli et al ., 1999 ), the hindlimb and pulmonary vasculature in cats ( Santiago et al ., 1995 ; Seyedi et al ., 1997 ) and human ocular tissues ( Ma et al ., 1996 ) and T lymphocytes ( Prat et al ., 1999 ). Factors implicated in B 1 receptor induction include bacterial endotoxin, pro‐inflammatory cytokines (e.g., interleukin‐1) as well as intracellular pathways regulating the cell response to environmental stress (e.g., the p38 MAP kinase and NF‐κB pathways) ( Bastian et al ., 1998 ; Larrivee et al ., 1998 ; Marceau et al ., 1998 ; Phagoo et al ., 1999 ; Prat et al ., 1999 ; Sardi et al ., 1998 ; Schanstra et al ., 1998 ; Tsukagoshi et al ., 1999 ). In turn, B 1 receptor stimulation may activate further these same pathways ( Campos et al ., 1999 ; Naraba et al ., 1998 ; Schanstra et al ., 1998 ; Tsukagoshi et al ., 1999 ).…”

Section: Discussionmentioning

confidence: 99%

“…Factors implicated in B 1 receptor induction include bacterial endotoxin, pro‐inflammatory cytokines (e.g., interleukin‐1) as well as intracellular pathways regulating the cell response to environmental stress (e.g., the p38 MAP kinase and NF‐κB pathways) ( Bastian et al ., 1998 ; Larrivee et al ., 1998 ; Marceau et al ., 1998 ; Phagoo et al ., 1999 ; Prat et al ., 1999 ; Sardi et al ., 1998 ; Schanstra et al ., 1998 ; Tsukagoshi et al ., 1999 ). In turn, B 1 receptor stimulation may activate further these same pathways ( Campos et al ., 1999 ; Naraba et al ., 1998 ; Schanstra et al ., 1998 ; Tsukagoshi et al ., 1999 ). B 1 receptors may also interact with cytokines to promote further B 1 receptor up‐regulation ( Phagoo et al ., 1999 ).…”

Section: Discussionmentioning

confidence: 99%

Endotoxin sensitization to kinin B₁ receptor agonist in a non‐human primate model: haemodynamic and pro‐inflammatory effects

deBlois

Horlick

2001

British J Pharmacology

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1 Although endotoxaemia induces kinin B 1 receptors in several animal models, this condition is not documented in primates. This study examined the up-regulation of haemodynamic and proin¯ammatory responses to the B 1 agonist des-Arg 10 -kallidin (dKD) in a non-human primate model. 2 Green monkeys (Cercopithecus aethiops St Kitts) received lipopolysaccharide (LPS; 90 mg kg 71 ) or saline intravenously. After 4 h, anaesthetized monkeys were canulated via the carotid artery to monitor blood pressure changes following intra-arterial injections of dKD or the B 2 agonist bradykinin (BK). Oedema induced by subcutaneous kinin administration was evaluated as the increase in ventral skin folds in anaesthetized monkeys injected with captopril at 4 h to 56 days post-LPS. 3 LPS increased rectal temperature but did not a ect blood pressure after 4 h. dKD reduced blood pressure (E max : 27+4 mmHg; EC 50 : 130 pmol kg 71 ) and increased heart rate (E max : 33 b.p.m.) only after LPS. In contrast, the dose-dependent fall in blood pressure with BK was comparable in all groups. The selective B 1 antagonist [Leu 9 ]dKD (75 ng kg 71 min 71 , intravenously) abolished responses to dKD but not BK. 4 dKD injection induced oedema dose-dependently (2.4+0.1 mm at 150 nmol) only following LPS (at 4 h to 12 days but not 56 days). In contrast, BK-induced oedema was present and stable in all monkeys. Co-administration of [Leu 9 ]dKD (150 nmol) signi®cantly reduced oedema induced by dKD (50 nmol). 5 These results suggest LPS up-regulation of B 1 receptor e ects in green monkeys. This non-human primate model may be suitable for testing new, selective B 1 antagonists with therapeutic potential as anti-in¯ammatory agents.

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“…Due to B 1 -receptor upregulation, rat paw oedema induced by desArg 9 BK has been found to be augmented by IL-1β or TNFα pretreatment [174]. IL-1β causes the upregulation of B 2 receptors in bronchial smooth muscle cells [110,178], human decidua [152,179] and synovial cells [180]. On the other hand, the expression of kinin B 2 receptor gene may be induced by chemokines leading to the upregulation of B 2 receptors.…”

Section: Immune Systemmentioning

confidence: 99%

“…All these effects on fibroblasts cells suggest that endogenous kinins may play a role in the tissue repair and wound healing process, since mitosis and collagen production of fibroblasts are parameters of wound healing [188]. As mentioned above, chemokines such as IL-1α, IL-1β, IL-2, IL-8 and TNF have been found to increase kinin effects due to up-regulations of both B 1 and B 2 receptors [157,[167][168][169][170][171][175][176][177][178]. Proliferative effects of kinins are not only limited to direct stimulation of cells, but also require the secretion of a variety of tissue growth factors and chemokines which are involved in tissue repair.…”

Section: Tissue Repair and Cell Proliferationmentioning

confidence: 99%

Kinin Receptors and Their Antagonists as Novel Therapeutic Agents

Öztürk

2001

CPD

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Plasma kinins are a family of peptides which play an important role in a variety of pathophysiological conditions. As a consequence of the progress in the area of kinin receptors, specific kinin receptor antagonists will be available in near future in order to provide more selective therapeutic modalities for the treatment of diseases such as asthma, cardiovascular diseases, inflammation, pain, etc. Although the initial observation leading to discovery of kinins has been performed in 1909, important progress on the development of specific kinin receptor antagonists has been made in last two decades. This review emphasizes the physiological functions of kinins along with their receptor subtypes and post-receptor events in the cellular signaling. In this article, the latest developments in the kinin receptor antagonists including nonpeptide ones have been reviewed.

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Regulation by Interleukin-1β of Gene Expression of Bradykinin B1 Receptor in MH-S Murine Alveolar Macrophage Cell Line

Cited by 20 publications

References 30 publications

Pharmacological, Pharmacokinetic, and Primate Analgesic Efficacy Profile of the Novel Bradykinin B₁ Receptor Antagonist ELN441958

Pharmacological, Pharmacokinetic, and Primate Analgesic Efficacy Profile of the Novel Bradykinin B₁ Receptor Antagonist ELN441958

Endotoxin sensitization to kinin B₁ receptor agonist in a non‐human primate model: haemodynamic and pro‐inflammatory effects

Kinin Receptors and Their Antagonists as Novel Therapeutic Agents

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Regulation by Interleukin-1β of Gene Expression of Bradykinin B1 Receptor in MH-S Murine Alveolar Macrophage Cell Line

Cited by 20 publications

References 30 publications

Pharmacological, Pharmacokinetic, and Primate Analgesic Efficacy Profile of the Novel Bradykinin B1 Receptor Antagonist ELN441958

Pharmacological, Pharmacokinetic, and Primate Analgesic Efficacy Profile of the Novel Bradykinin B1 Receptor Antagonist ELN441958

Endotoxin sensitization to kinin B1 receptor agonist in a non‐human primate model: haemodynamic and pro‐inflammatory effects

Kinin Receptors and Their Antagonists as Novel Therapeutic Agents

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Product

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Pharmacological, Pharmacokinetic, and Primate Analgesic Efficacy Profile of the Novel Bradykinin B₁ Receptor Antagonist ELN441958

Pharmacological, Pharmacokinetic, and Primate Analgesic Efficacy Profile of the Novel Bradykinin B₁ Receptor Antagonist ELN441958

Endotoxin sensitization to kinin B₁ receptor agonist in a non‐human primate model: haemodynamic and pro‐inflammatory effects