134
fCgA4–16 frog CgA4–16
fCgA47–66 frog CgA47–66
ISO Isoproterenol
NO Nitric Oxide
NOS Nitric Oxide Synthase
PI3K Phosphatidyl 3-kinase
PKG Protein Kinase G
PLN Phospholamban
PTx Pertussis toxin
SERCA2a Sarcoplasmic Reticulum Ca2+−ATPase
VS-1 Vasostatin 1 (CgA1–76)
VS-2 Vasostatin 2 (CgA1–113)
VSs Vasostatins
W7 N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide
1 Introduction
Chromogranins A (CgA) is a member of the granin family, a group of acidic soluble
proteins, found in secretory granules of endocrine, neuroendocrine, and neuronal
cells, which are co-stored and co-released with hormones, neurotransmitters, and/or
amines in response to specific stimuli. CgA, the first member of the family to be
isolated and characterized (Banks and Helle 1965 ), is a protein of 48 kDa identified
almost five decades ago, extensively studied as to its expression, structure and func-
tion. Soon after the first sequencing of bovine CgA (Iacangelo et al. 1986 ), many
immunological and sequence studies have shown its ubiquitous distribution through-
out the animal world, from invertebrates to mammals, remarking its notable phylo-
genetic conservation. CgA is present in teleost fish (Deftos et al. 1987 ), amphibians
(Reinecke et al. 1991 ), reptiles (Trandaburu et al. 1999 ), birds (Reinecke et al.
1991 ), humans, pigs and rats (Tota et al. 2007 ; Helle et al. 2007 ). Among inverte-
brates, the occurrence of CgA has been reported in the nematode parasite Ascaris
suum (Smart et al. 1992 ), the protozoan Paramecium tetraurelia (Peterson et al.
1987 ), and in coelenterates (Barkatullah et al. 1997 ).
Studies performed during the last 25 years evidenced the presence of CgA in the
heart of several mammalian and non mammalian vertebrates. It was identified in the
cardiac conduction system and in the atrial myoendocrine granules of the rat heart
(Steiner et al. 1990 ; Weiergraber et al. 2000 ) and in the ventricular myocardium of
the human heart (Pieroni et al. 2007 ). Both in humans and rodents, it was found to
be co-stored and co-secreted with catecholamines (CAs) and natriuretic peptides
(Steiner et al. 1990 ; Pieroni et al. 2007 ; Biswas et al. 2010 ). In non-mammalian
vertebrates, CgA expression was detected in the secretory granules of frog atrial
myocytes (Krylova 2007 ).
A. Gattuso et al.