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Autoradiographic visualization of angiotensin-converting enzyme in rat brain with (/sup 3/H)captopril: localization to a striatonigral pathway

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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The authors have visualized angiotensin-converting enzyme (ACE; dipeptidyl carboxypeptidase, peptidylpeptide hydrolase, EC 3.4.15.1) in rat brain by in vitro (/sup 3/H)captopril autoradiography. (/sup 3/H)Captopril binding to brain slices displays a high affinity (K/sub d/ = 1.8 x 10/sup -9/ M) and a pharmacological profile similar to that of ACE activity. Very high densities of (/sup 3/H)captopril binding were found in the choroid plexus and the subfornical organ. High densities were present in the caudate putamen and substantia nigra, zona reticulata. Moderate levels were found in the entopeduncular nucleus, globus pallidus, and median eminence of the hypothalamus. Lower levels were detectable in the supraoptic and paraventricular nuclei of the hypothalamus, the media habenula, the median preoptic area, and the locus coeruleus. Injection of ibotenic acid or colchicine into the caudate putamen decreased (/sup 3/H)captopril-associated autoradiographic grains by 85% in the ipsilateral caudate putamen and by > 50% in the ipsilateral substantia nigra. Thus, ACE in the substantia nigra is located on presynaptic terminals of axons originating from the caudate putamen, and ACE in the caudate putamen is situated in neuronal perikarya or at the terminals of striatal interneurons. The lack of effect of similar injections into the substantia nigra confirmed that the caudate putamen injections did not cause trans-synaptic changes. The presence of (/sup 3/H)captopril binding is consistent with an ACE-mediated production of angiotensin II in some brain regions. Although (/sup 3/H)captopril autoradiography reveals ACE in a striatonigral pathway, there is no evidence for angiotensin II involvement in such a neuronal pathway. 26 references, 4 figures, 2 tables.

Research Organization:
Johns Hopkins Univ. School of Medicine, Baltimore, MD
OSTI ID:
6137354
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 81:5; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALKALOIDS
AMINES
AMINO ACIDS
ANGIOTENSIN
ANIMALS
ANTIMITOTIC DRUGS
ANTIPYRETICS
AUTORADIOGRAPHY
AZOLES
BIOLOGICAL PATHWAYS
BODY
BRAIN
CARBOXYLIC ACIDS
CARBOXYPEPTIDASES
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL BONDS
COLCHICINE
DRUGS
ENZYME ACTIVITY
ENZYMES
GLOBULINS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROLASES
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PROLINE
PROTEINS
PYRROLES
PYRROLIDINES
RATS
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOCONSTRICTORS
VERTEBRATES