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
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
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.