Autoradiographic comparison of the distribution of the neutral endopeptidase enkephalinase and of. mu. and delta opioid receptors in rat brain
The neutral endopeptidase EC 3.4.24.11, also designated enkephalinase, has been visualized by in vitro autoradiography using the tritiated inhibitor (/sup 3/H)-N-((2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)glycine, ((/sup 3/H)HACBO-Gly). Specific binding of (/sup 3/H)HACBO-Gly corresponding to 85% of the total binding to brain slices was inhibited by 1 ..mu..M thiorphan, a selective inhibitor of enkephalinase, but remained unchanged in the presence of captopril, a selective inhibitor of angiotensin-converting enzyme. Very high levels of (/sup 3/H)HACBO-Gly binding were found in the choroid plexus and the substantia nigra. High levels were present in the caudate putamen, globus pallidus, nucleus accumbens, olfactory tubercle, and in the substantia gelatinosa of the spinal cord. The distribution of enkephalinase was compared to that of ..mu.. and delta opioid receptors, selectively labeled with (/sup 3/H)Tyr-D-Ala-Gly-MePhe-glycinol and (/sup 3/H)Try-D-Thr-Gly-Phe-Leu-Thr, respectively. In the caudate putamen, (/sup 3/H)HACBO-Gly binding overlapped the clustered ..mu.. sites but appeared more closely related to the diffusely distributed delta sites. The association of enkephalinase with delta and ..mu.. opioid receptors in these areas is consistent with the observed role of the enzyme in regulating the effects of opioid peptides in striatal dopamine release and analgesia, respectively. Except for the choroid plexus and the cerebellum, the close similarity observed in numerous rat brain areas between the distribution of enkephalinase and that of ..mu.. and/ or delta opioid binding sites could account for most of the pharmacological effects elicited by enkephalinase inhibitors.
- Research Organization:
- UER des Sciences Pharmaceutiques et Biologiques, Paris, France
- OSTI ID:
- 5559138
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 83:5
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BRAIN
AUTORADIOGRAPHY
PEPTIDE HYDROLASES
TISSUE DISTRIBUTION
TRITIUM COMPOUNDS
ENKEPHALINS
ENZYME INHIBITORS
PHARMACOLOGY
RATS
RECEPTORS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CENTRAL NERVOUS SYSTEM
DISTRIBUTION
DRUGS
ENDORPHINS
ENZYMES
HYDROLASES
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
RODENTS
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics