The angiotensin type 2 receptor of angiotensin II and neuronal differentiation: from observations to mechanisms

Abstract

The angiotensin II (Ang II) type 2 receptor (AT 2 ) is a member of the seven-transmembrane domain, G-protein coupled receptor family. This receptor is ubiquitously distributed in the fetus but, in most tissues, its expression dramatically falls in the first few hours after birth. Based on this observation, the hypothesis that this receptor could be involved in fetal development was raised and, over the past ten years, many studies have tried to identify a role for the AT 2 receptor using many different tissues and cell lines. To date, one of the major roles associated with the Ang II AT 2 receptor concerns its ability to induce neuronal differentiation. Indeed, in cells of neuronal origin, activation of the AT 2 receptor was shown to induce neurite outgrowth and elongation, modulate neuronal excitability, promote cellular migration and, in particular conditions, induce neuronal cell death. Regarding its signaling mechanisms, the AT 2 receptor still represents one of the most controversial G-protein coupled receptors since it does not stimulate the production of any of the classical second messengers. This review summarizes knowledge of the functions and the signaling mechanisms involved in the actions of the AT 2 receptor in neurons and cells of neuronal origin. Based on its altered expression in neurological disorders, a role for the AT 2 receptor in control of neuronal plasticity is proposed.

Role of the renin-angiotensin system in the development of the ureteric bud and renal collecting system

“…Our preliminary results indicate that AT 2 stimulates cell process formation in UB cells in vitro [33]. This observation is consistent with the ability of AT 2 to induce neurite outgrowth and elongation [75]. The ultimate effect of ANG II on UB branching may depend on the balance between AT 1 -and AT 2 -mediated actions, cellular context, temporal profiles of the local concentrations of ANG II in specific spatial microdomains or the ability to establish a concentration gradient during critical periods of branching morphogenesis.…”

Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

“…While AT 2 R expression is low in several adult tissues, there is a general consensus that AT 2 R promotes vasodilatation, growth inhibition, cell differentiation and apoptosis (de Gasparo et al 2000, St-Louis et al 2001, Gendron et al 2003. However, in the adrenal ZG, AT 2 R expression is maintained at a high level, even in the adult (Breault et al 1996, Frei et al 2001.…”

Angiotensin‐converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6‐hydroxydopamine rat model of Parkinsonism

“…Furthermore, in addition to the humoral RAS, all components of the RAS exist in many tissues (Ganong, 1994;Re, 2004). The brain possesses a local angiotensin system (Gendron et al, 2003;McKinley et al, 2003;Pan, 2004;Rodriguez-Pallares et al, 2004), and the results of previous studies have suggested that AII and its receptors play an important role in modulating striatal dopamine (DA) levels. Both AII and AII receptors as well as angiotensinogen and angiotensin-converting enzyme (ACE) have been observed in the striatum (Quinlan and Phillips, 1981;Brownfield et al, 1982;Chai et al, 1987;Allen et al, 1992Allen et al, , 1998, and AII stimulates the release of newly synthesized DA via angiotensin type 1 receptors (AT 1 ) located in the striatal DA terminals (Mendelsohn et al, 1993;Brown et al, 1996;Ge and Barnes 1996).…”