Résumés
Résumé
Hormis ses effets pro-inflammatoires, la bradykinine possède dorénavant le statut de neuromédiateur et de régulateur de plusieurs fonctions vasculaires et rénales. Des avancées récentes dévoilent des systèmes de signalisation atypiques et peu communs pour un récepteur couplé aux protéines G, lesquels pourraient expliquer les effets anti-prolifératif et anti-fibrosant de la bradykinine. L’étude de modèles génétiquement modifiés pour l’expression de ses récepteurs ou des enzymes de sa synthèse ou de sa dégradation, a permis de suggérer un rôle cardio- et néphro-protecteur à ce système. L’activation des récepteurs de la bradykinine participe aux mécanismes d’action des inhibiteurs de l’enzyme de conversion de l’angiotensine I qui sont des médicaments de choix dans le traitement des maladies cardiovasculaires et du diabète. Néanmoins, les études de la régulation et de la fonction des récepteurs de la bradykinine révèlent des divergences notables entre le système nerveux central et les tissus périphériques. En conséquence, un ciblage plus spécifique des récepteurs périphériques avec des molécules, agonistes ou antagonistes, qui ne passent pas la barrière hémato-encéphalique, s’impose comme nouvelle démarche thérapeutique.
Summary
In addition to being a pro-inflammatory mediator, bradykinin is now recognized as a neuromediator and regulator of several vascular and renal functions. New breakthroughs point to unusual and atypical signalling pathways for a G-protein coupled receptor that could explain the anti-proliferative and anti-fibrogenic effects of bradykinin. The availability of transgenic and knock out animal models for bradykinin receptors or bradykinin-synthesizing or -catabolic enzymes confirms these cardiac and renal protective roles for this peptide system. Bradykinin receptors are involved in the therapeutic action of angiotensin-1 converting enzyme inhibitors that are used in the treatment of arterial hypertension, heart failure and diabetes. Nevertheless, recent evidence highlights dissimilar mechanisms in the regulation and function of these receptors between the central nervous system and peripheral tissues. Therefore, the development of more specific bradykinin receptor agonists or antagonists devoid of central actions seems to evolve as a new therapeutic approach.
Parties annexes
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