Chromogranins from Cell Biology to Physiology and Biomedicine

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site of VS-1 on the membrane, Di Felice and collaborators ( 2006 ) used cardiomyo-
cytes three-dimensionally cultured in Matrigel (myocardial extracellular matrix:
ECM) exposed to Aurum conjugated hrCgA1−78 (Au-hrCgA1−78). They observed
by immunoglod technique that Au-hrCgA1−78 exclusively localizes outside the
plasma membrane of cardiomyocytes, at a distance between 16 and 25  nm. This
distance is characteristic of the interactions between ECM proteins and the cell.
This suggests that in vivo natural VS-1 acts via cell–ECM interactions. Two putative
domains of the human recombinant fragment could be considered for its binding to
either the cell membrane or ECM components: an RGD sequence at residues 43–45
(Gasparri et  al. 1997 ) and a net positively charged domain at residues 47–70
(Mandalà et al. 2005 ). However, the RGD site of CgA is not conserved among dif-
ferent species and its involvement in the regulation of cell–ECM interactions
remains to be proved.

VS-1 (1-76)

and

Chr(47-66)

CST

(344-364)

Serpinin

(403-431)

Gi/o

Proteins

Gi/o

Proteins

Gs

Proteins

NOS/NO

AC/cAMP

sGC/cGMP

PKG PKA

↑

adrenergicadrenergic

anti ET-1

Adrenergic-like

VS-1 (1-76)

CST

(344-364)

Serpinin

(403-431)

↓contractility contractility

Anti Anti

ChromograninA

Fig. 3 Representative scheme showing the physiological pathways activated by CgA-derived pep-
tides. Cardioinhibitory effects induced by Human VS1 (1–76), Chromofungin (47–66) and CST
involve the NOS/NO/cGMP/PKG pathway. Serpinin-dependent positive inotropism involves the
AD/cAMP/PKA pathway (Modified by Tota et al. 2014 )

Cardiac Physio-Pharmacological Aspects of Three Chromogranin A-Derived Peptides...