Involvement of insulin-regulated aminopeptidase and/or aminopeptidase N in the angiotensin IV-induced effect on dopamine release in the striatum of the rat.

Bart Stragier, Heidi Demaegdt, Dimitri De Bundel, Ilse Julia Smolders, Sophie Sarre, Georges Vauquelin, Guy Ebinger, Yvette Michotte, Patrick Vanderheyden

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29 Citaten (Scopus)

Samenvatting

Locally administered angiotensin IV causes a dose-dependent increase of the dopamine levels in the striatum of the rat. The aminopeptidase insulin-regulated aminopeptidase (IRAP) and/or aminopeptidase N(AP-N) are proposed to be involved in this effect since both enzymes are inhibited by angiotensin IV. In agreement with this hypothesis we demonstrate that by using the AP-N selective inhibitor 7B, about 60% of the aminopeptidase activity in striatal membranes could be attributed to AP-N (pKi=9.20). Higher concentrations of 7B are capable of inhibiting IRAP as well (pki= 7.26). Interestingly, IV-mediated effect in the striatum since 7N itself is not capable to induce dopamine release such as observed with angiotensin IV. However, 7B at a concentration selective for inhibition of AP-N (100 nM) potentiates the angiotensin IV-mediated increase of dopamine, suggesting that inhibition of AP-N lengthens the half-life of angiotensin IV. On the other hand, inhibition of both AP-N and IRAP by perfusion of 500 nM 7B completely abolishes the effect of angiotensin IV. We therefore hypothesize that the effect of angiotensin IV on dopamine release in the striatum is mediated via activation of IRAP and/or AP-N, possibly acting as receptors for angiotensin IV.
Originele taal-2English
Pagina's (van-tot)97-105
Aantal pagina's9
TijdschriftBrain Research
Volume1131
StatusPublished - 13 dec 2007

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