Binding, degradation and pressor activity of angiotensins II and III after aminopeptidase inhibition with amastatin and bestatin
In the metabolism of angiotensin peptides by tissue angiotensinases, aminopeptidases A, B, M and leucine aminopeptidase have been identified as being particularly effective. Because the inhibitory actions of amastatin (AM) and bestatin (BE) are relatively specific for these aminopeptidases, we have examined the effects of these inhibitors on the binding, degradation and pressor activity of angiotensin II (AII) and angiotensin III (AIII). Within 30 min at 37 degrees C, significant metabolism of /sup 125/I-AII and /sup 125/I-AIII by homogenates of a block of tissue containing hypothalamus, thalamus, septum and anteroventral third ventricle regions of the brain was observed. A majority of /sup 125/I-AIII metabolism was due to soluble peptidases, whereas that of /sup 125/I-AII primarily resulted from membrane-bound peptidases. AM, BE and reduced incubation temperatures significantly decreased the metabolism of /sup 125/I-AII and /sup 125/I-AIII. After appropriate adjustments to reflect the proportion of intact radioligand bound, temperature- or inhibitor-induced decreases in metabolism were matched by corresponding increases in specific binding. Heat-treated bovine serum albumin, as a nonspecific peptidase inhibitor, had no effect on either the metabolism or binding of the ligands used. In accordance with their actions in vitro, i.c.v. administration of AM and BE prolonged the pressor activity of subsequently applied AII and AIII. Unexpectedly, the amplitude of the pressor response to AIII was increased by BE, whereas that to AII was decreased by AM. The results of this study indicate that the metabolism of AII and AIII by aminopeptidases is relatively specific and acts to modulate the actions of these peptides.
- Research Organization:
- Washington State Univ., Pullman
- OSTI ID:
- 5841702
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 242:3; ISSN JPETA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOPEPTIDASES
ANGIOTENSIN
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BLOOD PRESSURE
BODY
BRAIN
CARBOXYLIC ACIDS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
GLOBULINS
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LEUCINE
MAMMALS
METABOLISM
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PEPTIDES
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
TRACER TECHNIQUES
VASOCONSTRICTORS
VERTEBRATES