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

Angiotensin (Ang)-(1-7) is an endogenous peptide hormone of the renin-angiotensin system which exerts diverse biological actions, some of them counterregulate Ang II effects. In the present study potential effect of Ang-(1-7) on phosphoinositide (PI) turnover was evaluated in neonatal rat brain. Cerebral cortex prisms of seven-day-old rats were preloaded with [(3)H]myoinositol, incubated with additions during 30 min and later [(3)H]inositol-phosphates (IPs) accumulation quantified. It was observed that PI hydrolysis enhanced 30% to 60% in the presence of 0.01 nM to 100 nM Ang-(1-7). Neither 10 nM [D-Ala(7)]Ang-(1-7), an Ang-(1-7) specific antagonist, nor 10 nM losartan, an angiotensin II type 1 (AT(1)) receptor antagonist, blocked the effect of 0.1 nM Ang-(1-7) on PI metabolism. The effect of 0.1 nM Ang-(1-7) on PI hydrolysis was not reduced but it was even significantly increased in the simultaneous presence of [D-Ala(7)]Ang-(1-7) or losartan. PI turnover enhancement achieved with 0.1 nM Ang-(1-7) decreased roughly 30% in the presence of 10 nM PD 123319, an angiotensin II type 2 (AT(2)) receptor antagonist. The antagonists alone also enhanced PI turnover. Present findings showing an increase in PI turnover by Ang-(1-7) represent a novel action for this peptide and suggest that it exerts a function in this signaling system in neonatal rat brain, an effect involving, at least partially, angiotensin AT(2) receptors.