Récepteurs de l'angiotensine II

Abstract

L'angiotensine II est une hormone peptidique qui exerce une multitude d'actions biologiques au niveau du système cardio-vasculaire, du rein et du système nerveux central. Les effets de l'hormone sont relayés par deux sous-types de récepteurs, AT 1 et AT 2, appartenant à la famille des récepteurs à sept domaines transmembranaires. Outre ses effets classiques, l'angiotensine II stimule la croissance de divers types cellulaires, notamment les myocytes cardiaques et les cellules musculaires lisses vasculaires. Dans ces dernières, cet effet hypertrophique est relayé par le récepteur AT 1 , puis par plusieurs seconds messagers e t un réseau complexe d'au moins trois cascades de protéine kinases : la p70 S6 kinase, les MAP kinases ERK1 /ERK2 et une tyrosine kinase. A l'inverse, des travaux récents suggèrent que la liaison de l' Ang II au récepteur de sous-type AT 2 pourrait exercer un effet inhibiteur sur la croissance de certaines cellules. Les mécanismes par lesquels le signal du récepteur AT 2 est transmis restent cependant inconnus.

Angiotensin II (Ang II) is a peptide hormone that evokes a wide range of biological actions on the cardiovascular, renal and central nervous systems. The effects of the hormone are initiated by its interaction with two pharmacologically distinct subtypes of receptors, designated AT1 and AT2. Both receptors belong to the superfamily of seven transmembrane domains receptors. In addition to its classical actions, Ang II exerts growth promoting effects on diverse cell types, such as vascular smooth muscle cells (SMC) and cardiac myocytes. In vascular SMC, Ang II induces cellular hypertrophy as a result of increased protein synthesis, but has no effect on cell proliferation. This trophic effect is mediated by the AT1 receptor subtype and results from regulatory changes at the levels of transcription and translation. The binding of Ang II to the AT1 receptor stimulates the production of various second messengers which then propagate the signal towards a complex network of protein kinases. We have shown that the enzymatic activation of three independent protein kinase cascades, p70 S6 kinase, ERK1/ERK2 subfamily of MAP kinases and a tyrosine kinase, is necessary for a full stimulatory effect of Ang II on protein synthesis. On the other hand, recent studies suggest that the interaction of Ang II with the AT2 receptor subtype might inhibit the growth of certain cell types. The signaling mechanisms of the AT2 receptor remain to be established. [References: 54]