221than serpinin (Koshimizu et al. 2011b). It was demonstrated that the enhanced
expression of PN-1 by serpinin was mediated through binding of the peptide to a
cognate receptor, which then increased cAMP (Fig. 8B). Addition of 8-bromo-
cAMP or forskolin also increased PN-1 expression (Fig. 8A). Enhancement of PN-1
expression by serpinin was inhibited by an inhibitor of protein kinase A (PKA),
622-amide, (Fig. 8C), as well as by mithramycin A, that inhibits the activity of the
transcription factor, sp1 (Fig. 8E). Furthermore, serpinin treatment of AtT20 cells
resulted in the movement of sp1 into the nucleus of the cells (Fig. 8D). Additionally,
luciferase reporter assay indicated that serpinin induced PN-1 expression by bind-
ing of sp1 to the promoter (Koshimizu et al. 2011a). Based on these findings, the
proposed mechanism of action of serpinin in inducing granule biogenesis in an
endocrine cell is summarized in the schematic in Fig. 9 (Kim et al. 2006 ).
Upon stimulated secretion of an endocrine cell, hormone and CgA-derived ser-
pinin peptides contained in dense-cored secretory granules are released and are
Fig. 6 Analysis of serpinin immunoreactivity (IR) in rat eye. (A) Serpinin-IR was found in cells in
the trigeminal ganglion, indicative of being a constituent of sensory neurons. (B) In the retina, which
is a part of the central nervous system, this serpinin-IR is expressed in the innermost part representing
glia (red fluorescence). (C) Serpinin was detected in the trigeminal ganglion (TG) and to a smaller
extent in the retina (RET) when these tissues we analyzed by HPLC-EIA for serpinin-IR
Serpinin Peptides: Tissue Distribution and Functions