title: In vivo characterization of the angiotensin-(1-7)-induced dopamine and gamma-aminobutyric acid release in the striatum of the rat.
abstract: 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 microm, 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 microm) 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 microm) 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Stragier
authors.forename: Ilina
authors.initials: I
authors.lastname: Hristova
authors.forename: Sophie
authors.initials: S
authors.lastname: Sarre
authors.forename: Guy
authors.initials: G
authors.lastname: Ebinger
authors.forename: Yvette
authors.initials: Y
authors.lastname: Michotte
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002845:Chromatography / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013451:Sulfonic Acids / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C092006:7-Ala-angiotensin (1-7); D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; C101968:EC 33; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D013451:Sulfonic Acids; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D005680:gamma-Aminobutyric Acid; D000803:Angiotensin I; C118790:angiotensin I (1-7); C081643:candesartan; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine