Role of calcitonin gene-related peptide and kinins in post-ischemic intestinal reperfusion

Madeddu, Paolo; Emanueli, Costanza; Salis, Maria Bonaria; Milia, Anna Franca; Stacca, Tiziana; Carta, Luisa; Pinna, Alessandra; Deiana, Maria Luisa; Gaspa, Leonardo

doi:10.1016/s0196-9781(01)00417-x

Cited by 12 publications

(8 citation statements)

References 20 publications

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“…Thus, activation of B 2 Rs may directly induce leukocyte migration and degranulation, and bradykinin may also act on leukocytes and/or endothelial cells to release proinflammatory mediators, such as cytokines and platelet-activating factor (8,30,31). Moreover, bradykinin acting on B 2 Rs may activate sensory nerves to release neuropeptides and potentiate the inflammatory response further (32,33). However, the protection afforded by blockade of B 2 Rs was only partial.…”

Section: Discussionmentioning

confidence: 99%

Role of Bradykinin B2 and B1 Receptors in the Local, Remote, and Systemic Inflammatory Responses That Follow Intestinal Ischemia and Reperfusion Injury

Souza¹,

Lomez

Pinho³

et al. 2004

The Journal of Immunology

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The administration of bradykinin may attenuate ischemia and reperfusion (I/R) injury by acting on B2Rs. Blockade of B2R has also been shown to ameliorate lesions associated with I/R injury. In an attempt to explain these contradictory results, the objective of the present work was to investigate the role of and interaction between B1 and B2 receptors in a model of intestinal I/R injury in mice. The bradykinin B2R antagonist (HOE 140) inhibited reperfusion-induced inflammatory tissue injury and delayed lethality. After I/R, there was an increase in the expression of B1R mRNA that was prevented by HOE 140. In mice that were deficient in B1Rs (B1R−/− mice), inflammatory tissue injury was abrogated, and lethality was delayed and partially prevented. Pretreatment with HOE 140 reversed the protective anti-inflammatory and antilethality effects provided by the B1R−/− phenotype. Thus, B2Rs are a major driving force for B1R activation and consequent induction of inflammatory injury and lethality. In contrast, activation of B2Rs may prevent exacerbated tissue injury and lethality, an effect unmasked in B1R−/− mice and likely dependent on the vasodilatory actions of B2Rs. Blockade of B1Rs could be a more effective strategy than B2 or B1/B2 receptor blockade for the treatment of the inflammatory injuries that follow I/R.

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Section: Discussionmentioning

confidence: 99%

Role of Bradykinin B2 and B1 Receptors in the Local, Remote, and Systemic Inflammatory Responses That Follow Intestinal Ischemia and Reperfusion Injury

Souza¹,

Lomez

Pinho³

et al. 2004

The Journal of Immunology

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“…The B 1 antagonist des-Arg 9 ,leu 8 -BK has been reported to inhibit the capsaicin-induced mouse ear edema by modulation of neurogenic inflammation (Mantione and Rodriguez, 1990). B 1 antagonists also block inflammation-like hypotension and plasma protein infiltration of the intestinal wall, observed during mesenteric postischemic reperfusion in the anesthetized rat, presumably regulated by a neurogenic reflex response (Madeddu et al, 2001). Likewise, SSR240612 caused a significant …”

Section: Discussionmentioning

confidence: 99%

SSR240612 [(2R)-2-[((3R)-3-(1,3-Benzodioxol-5-yl)-3-{[(6-methoxy-2-naphthyl)sulfonyl]amino}propanoyl)amino]-3-(4-{[2R,6S)-2,6-dimethylpiperidinyl]methyl}phenyl)-N-isopropyl-N-methylpropanamide Hydrochloride], a New Nonpeptide Antagonist of the Bradykinin B₁Receptor: Biochemical and Pharmacological Characterization

Gougat

Ferrari²,

Sarran³

et al. 2004

J Pharmacol Exp Ther

111

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The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B 1 receptor, SSR240612 [(2R)-2-[((3R)The compound selectivity for B 1 versus B 2 receptors was in the range of 500-to 1000-fold. SSR240612 inhibited Lys 0 -desAr 9 -BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC 50 of 1.9 nM. It also antagonized des-Arg 9 -BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA 2 of 8.9and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited desArg 9 -BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B 1 receptor antagonist.Kinins are 9 to 11 amino acid peptides known to be important mediators of pain, inflammation, and cardiovascular homeostasis. They are released in injured tissues from kininogen by activation of plasma or tissue kallikreins (Bhoola et al., 1992). Kinins exert their biological activities via the activation of two subtypes of G-protein coupled receptors, denoted B 1 and B 2 receptors (Regoli and Barabe, 1980;Regoli et al., 1998). Bradykinin (BK) and Lys 0 -BK are natural endogenous agonists of bradykinin B 2 receptors, whereas their kininase I-hydrolyzed metabolites des-Arg 9 -BK and Lys 0 -des-Arg 9 -BK are specific agonists of bradykinin B 1 receptors. B 1 peptide antagonists were obtained by replacing the C-terminal Phe residue of agonists by Leu. Human and rabbit B 1 receptors have a higher affinity for Lys 0 -desArticle, publication date, and citation information can be found at

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“…The mechanisms by which B 2 receptor activation facilitates inflammatory injury appears to be multiple, including the direct induction of leukocyte migration and degranulation, and the induction of the secondary release of proinflammatory mediators, such as cytokines and PAF (Koyama et al 1998, Calixto et al 2000. One interesting possibility to explain the effects of bradykinin acting on B 2 receptors in the system is that this mediator may activate sensory nerves to release neuropeptides and potentiate the inflammatory response further (Averbeck & Reeh 2001, Madeddu et al 2001. We have previously shown that neuropeptides acting via NK1 receptors are important for intestinal ischemia and reperfusion injury (Souza et al 2002a).…”

Section: Kallikrein-kinin Systemmentioning

confidence: 99%

The balance between the production of tumor necrosis factor-alpha and interleukin-10 determines tissue injury and lethality during intestinal ischemia and reperfusion

Souza

Teixeira

2005

Mem. Inst. Oswaldo Cruz

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Role of calcitonin gene-related peptide and kinins in post-ischemic intestinal reperfusion

Cited by 12 publications

References 20 publications

Role of Bradykinin B2 and B1 Receptors in the Local, Remote, and Systemic Inflammatory Responses That Follow Intestinal Ischemia and Reperfusion Injury

Role of Bradykinin B2 and B1 Receptors in the Local, Remote, and Systemic Inflammatory Responses That Follow Intestinal Ischemia and Reperfusion Injury

The balance between the production of tumor necrosis factor-alpha and interleukin-10 determines tissue injury and lethality during intestinal ischemia and reperfusion

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