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in the motor activities, by carrying information from the primary motor cortex to the
ipsilateral pontine nucleus in the ventral pons via corticopontine fibers and through
middle cerebellar peduncule to the contralateral cerebellum (Brodal and Bjaalie 1992 ;
Cicirata et al. 2005 ). Additionally, pGlu-serpinin has been found in the olfactory bulb
(Fig. 5C) primarily in the olfactory nerve layer (ONL) and the glomerular layer (GL)
which is enriched in nerve terminals, suggesting that pGlu-serpinin may be released
as a neurotransmitter or neuromodulator in the olfactory system.
4.3 Expression and Localization of Serpinin Peptides
in the Eye
In addition to the central nervous system, serpinin peptides have been found to be
present in the peripheral nervous system. In the rat peripheral nervous system, ser-
pinin immunoreactvity has been detected in abundance in cells in the trigeminal
ganglion which is the cranial sensory ganglion (Fig. 6A), indicating that it is a con-
stituent of sensory neurons. Since the peptide is expressed in small to medium-sized
cells with a diameter of 20–30 μm in this ganglion, the sensory nerves projecting to
target tissues must represent predominantly unmyelinated C-fibers which arise from
such cells. In the retina, which is a part of the central nervous system, this peptide is
atypically expressed in the innermost part representing glia (Fig. 6B). With respect
to the molecular form, only free serpinin has been detected in the trigeminal gan-
glion (Fig. 6C, TG) which indicates that exclusively free serpinin is present in sen-
sory nerves originating from this ganglion and that there exists a pronounced
processing of chromogranin A, already at the site of synthesis. Although in lessor
amounts, free serpinin also predominates in the retina (Fig. 6C, RET). Very small
amounts of serpinin-RRG may also be present in the trigeminal ganglion and the
retina (Fig. 6C).
5 Role of Serpinin and pGlu-Serpinin in Granule Biogenesis
Early studies showed that AtT20 cells treated with antisense CgA RNA to down-
regulate CgA expression (Fig. 7A,B; Kim et al. 2001 ) resulted in a decrease in
dense core secretory granule biogenesis (Fig. 7C; Kim et al. 2001 ), in a dose depen-
dent manner (Fig. 7D; Kim et al. 2001 ). To determine the mechanism by which CgA
up-regulates secretory granule biogenesis, conditioned medium from AtT20 cells
were analyzed. A CgA-derived peptide, serpinin was identified which enhanced
secretory granule biogenesis (See Introduction and Expression of serpinin sections).
Serpinin and pGlu-serpinin are both found in the secretion medium of AtT20 cells.
When these peptides were added to the medium of AtT20 cells, the expression of a
protease inhibitor, PN-1 was increased, with pGlu-serpinin being much more potent
Y. PengfiLoh et al.