Effects of aminopeptidase inhibition on the half-lives of [125I]angiotensins in the cerebroventricles of the rat.
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.
Dewey
A L
AL
Department of Veterinary Anatomy, Washington State University, Pullman 99164.
Wright
J W
JW
Hanesworth
J M
JM
Harding
J W
JW
D000626:Aminopeptidases / Q000378:metabolism*; D000804:Angiotensin II / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents; D002552:Cerebral Ventricles / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006207:Half-Life; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides; D051381:Rats; D011919:Rats, Inbred Strains
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D010455:Peptides; D000804:Angiotensin II; C016977:amastatin; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex