Phosphoinositide hydrolysis increase by angiotensin-(1-7) in neonatal rat brain

G. RODRIGUEZ DE LORES ARNAIZ; S. PEREYRA-ALFONSO; C. PEÑA

Portland, Oregon, USA

Congreso; 37th Annual Meeting of the American Society for Neurochemistry; 2006

American Society for Neurochemistry

Ang-(1-7) is an endogenous peptide hormone of the renin-angiotensin system which exerts diverse biological actions some of them involving noradrenergic system. Since the ability of norepinephrine to modify phosphoinositide (PI) turnover has been previously described, the purpose of this study was to evaluate potential effect of Ang-(1-7) on such signalling system. Neonatal rat brain prisms were incubated with [3H]myoinositol in Krebs-Henseleit buffer during 60 min. Then, drugs were added and incubation continued for 30 min. Reaction was stopped with cloroform/methanol and [3H]inositol-phosphates (IPs) accumulation was quantified. It was observed an enhancement of PI hydrolysis, which ranged from 30% to 60% in the presence of 0.01 nM to 100 nM Ang-(1-7). Since biological actions of Ang-(1-7) are blocked with [D-Ala7]Ang-(1-7), experiments with peptide were also carried out. It was observed that with 0.1 nM Ang-(1-7) IPs accumulation attained 161 ± 26.5% (n = 8), a value which was even higher (213 ± 23.5%, n = 5; P < 0.01) in the presence of 10nM [D-Ala7]Ang-(1-7). This antagonist alone was likewise able to increase PI turnover (153 ± 5.1%, n =3). Results indicate that Ang-(1-7) is able to modify cell signalling system mediated by PI hydrolysis, an effect most likely independent of Ang-(1-7) receptor which is blocked by [D-Ala7]Ang-(1-7).