First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [I-125]RB 129

Citation
F. Noble et al., First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [I-125]RB 129, NEUROSCIENC, 105(2), 2001, pp. 479-488
Citations number
64
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROSCIENCE
ISSN journal
03064522 → ACNP
Volume
105
Issue
2
Year of publication
2001
Pages
479 - 488
Database
ISI
SICI code
0306-4522(2001)105:2<479:FDADOA>2.0.ZU;2-A
Abstract
The selective and potent aminopeptidase N inhibitor [I-125]RB 129 has been used for the radioantographic localization of this enzyme in rat brain, spi nal cord and intestine. Brain microvessels and intestine brush-border cells were shown to present a high concentration of aminopeptidase N. Moreover, a labeling of various brain structures was observed. A very high level of b inding occurred in the meninges, choroid plexus, pineal gland, paraventricu lar nucleus and pituitary gland. Moderate to high labeling was also observe d in the cortex, caudate-putamen, subthalamic nucleus, central periaqueduct al gray, thalamus, as well as in the dorsal and ventral horn of the spinal cord, which are known to contain a high concentration of enkephalins, opioi d receptors and neutral endopeptidase. This co-localization confirms the ph ysiological implication of aminopeptidase N in the inactivation of enkephal ins accounting for the requirement of dual inhibition of neutral endopeptid ase and aminopeptidase N to observe highly significant morphine-like effect s induced by the protected endogenous opioid peptides. Aminopeptidase N was also visualized in moderate to high levels in other brain structures such as the hippocampus, nucleus accumbens, substantia nigra, hypothalamus (dors omedial and ventromedial nuclei), raphe nucleus, pontine nucleus, inferior olive, and in high concentration in the granular layer of cerebellum. In summary, aminopoptidase N has been visualized for the first time in nume rous brain areas using the selective inhibitor [I-125]RB 129. This iodinate d probe could allow the ey vivo and in vivo localization of aminopeptidase N in various tissues to be investigated and may also be used to evaluate qu antitative changes in aminopeptidase N expression in pathological situation s. Aminopeptidase N, which preferably removes NH2-terminal neutral amino ac ids from peptides, has probably a host of substrates, Nevertheless, a certa in in vivo selectivity could be achieved by the presence of the enzyme in s tructures where the peptide effector and its receptors are also co-localize d. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.