NDLI: Autoradiographic comparison of the distribution of the neutral endopeptidase 'enkephalinase' and of mu and delta opioid receptors in rat brain.

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Autoradiographic comparison of the distribution of the neutral endopeptidase 'enkephalinase' and of mu and delta opioid receptors in rat brain.

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Autoradiographic comparison of the distribution of the neutral endopeptidase 'enkephalinase' and of mu and delta opioid receptors in rat brain.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hamel, E. Roques, B. P. Waksman, G. Fournié-zaluski, M. C.
Abstract	The neutral endopeptidase EC 3.4.24.11, also designated enkephalinase, has been visualized by in vitro autoradiography using the tritiated inhibitor [3H]-N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl] glycine, ([3H]HACBO-Gly). Specific binding of [3H]HACBO-Gly (Kd = 0.4 +/- 0.05 nM) corresponding to 85% of the total binding to brain slices was inhibited by 1 microM 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 [3H]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. Moderate densities were found in parts of the amygdala, the periaqueductal gray matter, the interpeduncular nucleus, and the molecular layer of the cerebellum. The distribution of enkephalinase was compared to that of mu and delta opioid receptors, selectively labeled with [3H]Tyr-D-Ala-Gly-MePhe-glycinol and [3H]Tyr-D-Thr-Gly-Phe-Leu-Thr, respectively. In the caudate putamen, [3H]HACBO-Gly binding overlapped the clustered mu sites but appeared more closely related to the diffusely distributed delta sites. High levels of enkephalinase and mu opioid binding sites were present at the level of the periaqueductal gray matter and in the substantia gelatinosa of the spinal cord, regions where only sparse delta opioid receptors could be detected. 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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	83
Language	English
Publisher	National Academy of Sciences
Publisher Date	1986-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Metabolism Endopeptidases Receptors, Opioid Spinal Cord Animals Autoradiography Brain Mapping In Vitro Techniques Neprilysin Receptors, Opioid, Delta Receptors, Opioid, Mu Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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