Résumés
Résumé
Les kinines sont des peptides autacoïdes (hormones locales) et des neuromédiateurs centraux impliqués dans le contrôle cardiovasculaire, l’inflammation et la douleur. Leurs effets sont relayés par deux types de récepteurs couplés aux protéines G: un récepteur B2, constitutif, et un récepteur B1, inductible en présence de cytokines, d’endotoxines ou de lésions tissulaires. Alors que le récepteur B2 contribue aux effets bénéfiques des inhibiteurs de l’enzyme de conversion de l’angiotensine-I utilisés dans le traitement des maladies cardiovasculaires, il participe à la phase aiguë de l’inflammation et de la douleur somatique et viscérale. Le récepteur B1 participe, quant à lui, à la phase chronique de ces réponses, et jouerait un rôle stratégique dans les maladies ayant une forte composante immune telles que l’arthrite rhumatoïde, la sclérose en plaques, le choc septique ou le diabète. Il posséderait également une dualité fonctionnelle, se manifestant par une action protectrice (vis-à-vis de la sclérose en plaques et du choc septique, par exemple) ou délétère (dans le cas de la douleur et de l’inflammation). Ainsi, l’utilisation d’antagonistes de ces récepteurs comme agents thérapeutiques nécessite une évaluation rigoureuse de leurs effets.
Summary
Kinins are autacoid peptides and central neuromediators involved in cardiovascular regulation, inflammation and pain. Their effects are mediated by two transmembrane G-protein-coupled receptors denoted as B1 and B2. While the B2 receptor is constitutive, the B1 receptor is inducible and up-regulated in the presence of cytokines, endotoxins or during tissue injury. The B2 receptor is believed to play an important role in the beneficial effects of angiotensin-1 converting enzyme inhibitors used in the treatment of cardiovascular diseases, yet it is involved in the acute phase of inflammation and of somatic and visceral pain. Conversely, the B1 receptor participates in the chronic phase of these responses and is likely to play a strategic role in diseases with a strong immune component such as rheumatoid arthritis, multiple sclerosis, septic shock and diabetes. A dual function for the B1 receptor is also reported in some pathologies in which it can exert either a protective (multiple sclerosis and septic shock) or harmful (pain and inflammation) effect. Therefore, the use of antagonists for these receptors as clinical therapeutic agents requires a rigorous evaluation of the potential side effects.
Parties annexes
Références
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