The endocrine role for chromogranin A: A prohormone for peptides with regulatory properties

Abstract

Chromogranin A (CgA) belongs to the granin family of uniquely acidic secretory proteins co-stored and co-secreted with other hormones and peptides in elements of the diffuse neuroendocrine system. The granins arise from different genes and are characterized by numerous sites for post-translational cleavage into shorter peptides with postulated regulatory properties. This review is directed towards endocrine aspects of CgA and its biologically active peptides. There is ample evidence from in vitro studies of distinct effects and targets for three CgA-derived peptides, vasostatin-I, pancreastatin and catestatin. Endocrine regulations are indicated from in vivo studies, consistent with the postulated prohormone function of CgA for peptides with regulatory properties. Most of the effects fit into patterns of direct or indirect, inhibitory modulations of major functions, implicating CgA peptides in regulation of calcium and glucose metabolism, cardiovascular functions, gastrointestinal motility and nociception, tissue repair, inflammatory responses and as host defense peptides in the first phase of microbial invasions.

The catecholamine release-inhibitory peptide catestatin (chromogranin A344-364) modulates myocardial function in fish

“…As first shown in the adrenal medulla, it is co-stored and co-released with catecholamines (CAs) from the secretory vesicles of the chromaffin cells (Takiyyuddin et al, 1990;Helle et al, 2007). CgA has also been detected in secretory granules of the heart.…”

The eel heart: multilevel insights into functional organ plasticity

“…As first shown in the adrenal medulla, it is co-stored and co-released with CAs from the secretory vesicles of the chromaffin cells (Helle et al, 2007). CgA is the precursor of several regulatory peptides (i.e.…”

“…Accordingly, the heart may become targeted at the same time by these blood-borne CAs and those released by both SNS terminals and cardiac chromaffin cells (Nilsson and Holmgren, 1992; Farrell and Jones, 1992), which might become harmful in the absence of local counter-regulatory mechanisms. As comparatively proposed in frog (Mazza et al, 2008) and rat (Angelone et al, 2008b) hearts, CgA may function as prohormone for inhibitory proteins that, if released under stressful conditions, might protect the organ from excessive excitatory stimuli, acting as anti-adreno-sympathetic stabilizers (Helle et al, 2007). It remains to be established whether and to what extent CgA and its derived peptides contribute to the stress resistance of the eel.…”

“…CgA is the precursor of several regulatory peptides (i.e. vasostatins, pancreastatin, catestatin and parastatin), generated by cell-, tissue-and species-specific proteolytic processes, most of which act as powerful inhibitors of endocrine secretion [see Helle et al (Helle et al, 2007) and references therein].Evidence from the past decade suggests that CgA-derived vasostatin 1 (VS-1) and catestatin (Cts) peptides represent fundamental players in the cardiovascular homeostasis, contributing to the humoral regulation of the vertebrate hearts (Mazza et al, 2010). The teleost heart is not an exception.…”

The Natural Antimicrobial Chromogranins/Secretogranins- Derived Peptides – Production, Lytic Activity and Processing by Bacterial Proteases

“…Neuroendocrine activities are reported from in vivo studies, with modulations of homeostatic processes, such as calcium regulation and glucose metabolism (Helle et al, 2007), cardiovascular functions ( Brekke et al, 2002;Corti et al, 2004), gastrointestinal motility (Amato et al, 2005;Ghia et al, 2004a), nociception ( Ghia et al, 2004b) tissue repair (Gasparri et al, 1997;Ratti et al, 2000), inflammatory responses (Ceconi et al, 2002; and as host defense agents during infections (Radek et al, 2008). During the past decade, our laboratory has characterized new antimicrobial CGs-derived peptides (Strub et al, 1996a,b;Metz-Boutigue et al, 1998;Lugardon et al, 2000Lugardon et al, , 2001Briolat et al, 2005;Helle et al, 2007) (Figure 3). Fig.…”