In vivo characterization of the angiotensin-(1-7)-induced dopamine and γ-aminobutyric acid release in the striatum of the rat

The effect of angiotensin (Ang)-1-7 on dopamine, gamma-aminobutyric acid ( GABA) and glutamate release in the striatum of the rat was examined using in vivo microdialysis. Ang-( 1 - 7) was administered locally in the striatum through the microdialysis probe. At a concentration of 100 mu m, Ang-( 1 - 7) caused a significant increase in extracellular dopamine and GABA but had no effect on glutamate release. The Ang-( 1 - 7)- induced dopamine release was blocked by EC33, an inhibitor of aminopeptidase A, an enzyme which converts Ang-( 1 - 7) into Ang-( 3 - 7), suggesting that this effect occurs after metabolism into Ang-( 3 - 7). Indeed, administration of Ang( 3 - 7) ( 10 - 100 mu m) into the striatum caused a more potent increase in the striatal dopamine release than Ang-( 1 - 7). Because Ang-( 3 7) is an inhibitor of insulin-regulated aminopeptidase ( IRAP) and because Ang IV, another IRAP inhibitor, also causes a concentration-dependent increase in dopamine in the rat striatum, IRAP may be involved in this effect. In contrast, EC33 had no effect on the Ang-( 1 - 7)- induced GABA increase but the GABA release was blocked by the putative AT(1-7) receptor antagonist A779 (0.1 mu m) and by the nitric oxide synthase inhibitor L-NAME ( 1 mm). These drugs could not block the effect of Ang-( 1 - 7) on the striatal dopamine release suggesting that only the observed effects on GABA release are mediated by the AT(1-7) receptor and / or are associated with a release of nitric oxide.