Chromogranins from Cell Biology to Physiology and Biomedicine

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secretory granules at the tips of processes and poised for secretion. pGlu-serpinin
was found to be secreted in a stimulated manner (Fig. 3C; Koshimizu et al. 2011b),
suggesting that it may play an extracellular role in signal transduction, as a neu-
rotransmitter or neuromodulator.

4 Distribution of Serpinin Peptides in Organs

and the Nervous System

4.1 Serpinin Peptides in the Adrenal Medulla and Heart

Serpinin peptides have been found in the mouse adrenal medulla which synthesizes
large amounts of CgA. HPLC analysis revealed the presence of pGlu-serpinin as the
major serpinin peptide, with lesser amounts of serpinin in adrenal medulla (Fig. 4A).
Serpinin peptides are also expressed in the heart. The major serpinin peptide in rat
heart is the C-terminal extended form: serpinin-RRG, with a significant amount of
pGlu-serpinin also present (Fig. 4B). When assayed by sandwich ELISA for pGlu-
serpinin, the concentration of this peptide reported in rat heart was 103.8 ± 14.7 pg/g
rat heart (Tota et al. 2012 ).

-0.05

0.00

0.05

500

0

293031323334353637383940

1000

1500

0.10

0.15

0.20

0.25

0.30

010203040

Absorbance (460 nm)

Serpinin

pGlu-Serpinin

Blank run

A.

Fraction # (min)

Adrenal extract

Serpinin-RRG

pGlu-Serpinin

B.

Fraction # (min)

Serpinin EIA

pGlu-serpinin EIA

(pGlu)-Serpinin (pg/ml)

Heart extract

Fig. 4 Analysis of serpinin-immunoreactivity (IR) in tissue. (A) High pressure liquid chromatog-
raphy (HPLC) followed by enzyme-linked immunoassay (EIA) analysis of mouse adrenal gland
extracts. Note the presence of two peaks consistent with the elution profile for serpinin and pGlu-
serpinin standards. (B) HPLC-EIA analysis of rat heart extract for serpinin-IR and pGlu-serpinin.
Note the presence of two peaks consistent with the elution profile of serpinin-RRG and pGlu-
serpinin standards. A shoulder that is evident on the serpinin-RRG peak is indicative of a small
amount of serpinin in this tissue. Note that two different HPLC systems were used to analyze these
extracts resulting in different elution profiles of the peptides (From Tota et al. 2012 )

Y. PengfiLoh et al.