Structure activity relationships for bradykinin antagonists on the inhibition of cytokine release and the release of histamine☆

Reißmann, Siegmund; Pineda, Felipe; Vietinghoff, Gabriele; Werner, H.; Gera, Lajos; Stewart, John M.; Paegelow, I.

doi:10.1016/s0196-9781(00)00171-6

Cited by 15 publications

(9 citation statements)

References 27 publications

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“…We had shown that bradykinin caused bronchoconstriction through activation of bradykinin B2 receptors (Polosa & Holgate, 1990) and that repeated challenge with this peptide also rapidly led to the development of tolerance (Polosa et al ., 1993b; Rajakulasingam et al ., 1993). Both bradykinin B2 and adenosine receptors have been identified on mast cells (Reissmann et al ., 2000; Sylvin et al ., 2001) and also on peptidergic nerves (Fox et al ., 1996; Chung, 2002), raising the possibility that adenosine and bradykinin share some common activation pathways possibly through the release of neuropeptides such as substance P or other neurokinins, which are known to activate mast cells for mediator secretion (Rajakulasingam et al ., 1994).…”

Section: Unusual Features Of Adenosine‐induced Bronchoconstrictionmentioning

confidence: 99%

The Quintiles Prize Lecture 2004: The identification of the adenosine A_2B receptor as a novel therapeutic target in asthma

Holgate

2005

British J Pharmacology

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Adenosine is a powerful bronchoconstrictor of asthmatic, but not normal, airways. In vitro studies on isolated human mast cells and basophils revealed that adenosine and selective analogues augmented inflammatory mediator release from mast cells by stimulating A 2 receptors. Pharmacological blockade of mast cell mediator release in vivo also attenuated adenosine-induced bronchoconstriction, as did theophylline, by adenosine A 2 receptor antagonism. Further in vitro studies revealed that the asthmatic response to adenosine is likely to be mediated via the A 2B subtype which is selectively antagonised by enprofylline. Studies in animal models, especially mice, have shown a close synergistic interaction between adenosine, Th2 and airway remodelling responses. The recent description of A 2B receptors on human airway smooth muscle cells that mediate cytokine and chemokine release and induce differentiation of fibroblasts into myofibroblasts strengthens the view that adenosine maybe more than an inflammatory mediator in asthma but also participates in airway wall remodelling in this disease. These data have provided a firm basis for developing adenosine A 2B receptor antagonists as a new therapeutic approach to this disease.

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Section: Unusual Features Of Adenosine‐induced Bronchoconstrictionmentioning

confidence: 99%

The Quintiles Prize Lecture 2004: The identification of the adenosine A_2B receptor as a novel therapeutic target in asthma

Holgate

2005

British J Pharmacology

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“…The lowest concentrations that antagonise the bradykinin-induced cytokine release were 10 -15 M [53,56].…”

Section: Bradykinin Receptor Antagonistsmentioning

confidence: 98%

“…Also, cyclization in the N-terminus destroys the activity of type 2 antagonists [53]. The combination of replacements at positions 2 and 7 as well as at additional sequence positions resulted in highly active antagonists, more hydrophobic and more stable against enzymatic degradation than compounds with Pro 2 [56].…”

Section: Bradykinin Receptor Antagonistsmentioning

confidence: 99%

“…Because bradykinin itself releases cytokines from mononuclear cells [56] and histamine from rat mast cells [56] the influence of bradykinin antagonists on both releasing actions was studied. Some cytokines and the biogenic amine histamine are compounds that strongly activate inflammation processes [56].…”

Section: Bradykinin Receptor Antagonistsmentioning

confidence: 99%

“…Some cytokines and the biogenic amine histamine are compounds that strongly activate inflammation processes [56]. This action of bradykinin analogues is contradictory to the antiinflammatory action of bradykinin antagonists.…”

Section: Bradykinin Receptor Antagonistsmentioning

confidence: 99%

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Development of Conformationally Restricted Analogues of Bradykinin and Somatostatin Using Constrained Amino Acids and Different Types of Cyclization

Reißmann

Imhof²

2004

CMC

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The structure-based design of peptide drugs requires the knowledge of the bioactive conformation. Studies on this receptor-bound 3D structure require linear or cyclic analogues with strongly reduced flexibility, but high biological activity, since only analogues with retained potency have preserved the bioactive conformation. Constrained amino acids containing double bonds or bulky substituents at the N(alpha)-, C(alpha)- and C(beta)-atom as well as at the aromatic ring atom were successfully applied to obtain potent and stable analogues of bradykinin and somatostatin, which due to their restricted conformation were suitable objects for conformational studies. Besides the generation of constrained cyclic analogues with improved biological and pharmacological properties, cyclic peptides were used as convenient models for the study of turn formations. Cyclization of the linear peptide bradykinin was performed by linking the N-terminus and the C-terminus, and in both bradykinin and somatostatin by cyclization using the amino acid side chains and by backbone cyclization. The later requires the introduction of N(alpha)-functionalised amino acids for ring closure which can be performed either through incorporation of N(alpha)-functionalised amino acids or dipeptide building units. Conformational analysis of a cyclic bradykinin analogue by means of NMR-studies together with molecular dynamics simulation led to a quasicyclic 3D structure with two turns and together with other 3D structures provided a pharmacophore model of bradykinin antagonists.

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New agents for the treatment of cancer-related fatigue

Burks¹

2001

Cancer

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Structure activity relationships for bradykinin antagonists on the inhibition of cytokine release and the release of histamine☆

Cited by 15 publications

References 27 publications

The Quintiles Prize Lecture 2004: The identification of the adenosine A_2B receptor as a novel therapeutic target in asthma

The Quintiles Prize Lecture 2004: The identification of the adenosine A_2B receptor as a novel therapeutic target in asthma

Development of Conformationally Restricted Analogues of Bradykinin and Somatostatin Using Constrained Amino Acids and Different Types of Cyclization

New agents for the treatment of cancer-related fatigue

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Structure activity relationships for bradykinin antagonists on the inhibition of cytokine release and the release of histamine☆

Cited by 15 publications

References 27 publications

The Quintiles Prize Lecture 2004: The identification of the adenosine A2B receptor as a novel therapeutic target in asthma

The Quintiles Prize Lecture 2004: The identification of the adenosine A2B receptor as a novel therapeutic target in asthma

Development of Conformationally Restricted Analogues of Bradykinin and Somatostatin Using Constrained Amino Acids and Different Types of Cyclization

New agents for the treatment of cancer-related fatigue

Contact Info

Product

Resources

About

The Quintiles Prize Lecture 2004: The identification of the adenosine A_2B receptor as a novel therapeutic target in asthma

The Quintiles Prize Lecture 2004: The identification of the adenosine A_2B receptor as a novel therapeutic target in asthma