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  • Title: Effects of aminopeptidase inhibition on the half-lives of [125I]angiotensins in the cerebroventricles of the rat.
    Author: Dewey AL, Wright JW, Hanesworth JM, Harding JW.
    Journal: Brain Res; 1988 May 17; 448(2):369-72. PubMed ID: 3378160.
    Abstract:
    Anesthetized Sprague-Dawley rats fitted with intracerebroventricular (i.c.v.) cannulas were infused with one of the aminopeptidase inhibitors, amastatin or bestatin, over a 5-min period. After infusion, 1-2 X 10(6) cpm of [125I]angiotensin II ([125I]AII) or [125I]angiotensin III ([125I]AIII) was injected through the same cannula. The rats were subsequently killed 60 s later by focused microwave irradiation which instantaneously terminated further [125I]angiotensin metabolism. HPLC analysis of the extracted [125I]angiotensin and metabolic products allowed for the calculation of t1/2s of disappearance for the parent peptides. Both inhibitors effectively lengthened the half-lives of [125I]AII and [125I]AIII. Bestatin, which is considered a selective aminopeptidase B blocker, had a more pronounced effect on [125I]AIII metabolism, while amastatin, a selective aminopeptidase A inhibitor, was better at slowing [125I]AII degradation. The results indicate that amastatin and bestatin are very effective blockers of the cerebroventricular metabolism of angiotensins but are only marginally selective with regard to AII and AIII.
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