ANGIOTENSIN II RECEPTORS IN RAT CEREBELLUM: RECEPTOR LOCALIZATION AND SIGNAL TRANSDUCTION PATHWAYS

MARIA ELENA ARCE, SUSANA SANCHEZ, LEONARDO R. SEGUIN AND GLADYS M. CIUFFO

Santa Cruz, CHILE

Congreso; V international Meeting of the Latin American Society for Developmental Biology; 2010

The classical effects of Ang II are well known but new evidences involve this peptide in development. Interpretation of the function of Ang II in cerebellum necessitates a thorough understanding about the localization and signal transduction of Ang II receptors. A clear complementary pattern of AT1 and AT2 binding labeled by [125I]Ang II was  observed on adjacent layers in young rats within the cerebellar cortex. By using Zebrin II and Calbindin markers of the Purkinje cells (PCs), we demonstrated that AT2 receptors co-localized with the monolayer PCs, in correspondence with the well-defined layer observed in autoradiography at differential developmental stages. Blockade of AT2 receptors with PD123319 during late pregnancy caused a lost of AT2 binding in the external granular layer (EGL) in P0. Histological analysis evidenced an enlarged EGL in cerebellum. It is well known that PCs migrate early during fetal stage toward the cerebellar cortex. Aiming to elucidate the non-classical signaling pathway of AT2 receptors in hindbrain we selected a critical rat stage PND15. SHP-1 associates to AT2 receptors by Ang II stimulation. Immunocomplexes obtained with anti-AT2 or anti-SHP-1 exhibited PTPase activity, blocked by PD123319 or PP2. Both immunocomplexes contained c-Src and PP2 blocked SHP-1 tyr-phosphorylation as well as activation and association SHP-1 to c-Src. Taken together, the localization of AT2 receptors in the PCs, the effect of blockade during late pregnancy on the development of the cerebellar cortex and the signal transduction, a potential role for AT2 receptors can be assigned on neuronal migration and cerebellar cortex organization.