Chromogranin A N-terminal fragments vasostatin-1 and the synthetic CGA 7–57 peptide act as cardiostatins on the isolated working frog heart

Endothelium-derived nitric oxide mediates the antiadrenergic effect of human vasostatin-1 in rat ventricular myocardium

“…It has indeed been shown that the negative inotropism induced by VS-1 in isolated frog (12) and eel (19) hearts is, at least in part, dependent on the availability of K ϩ channels, since it was abolished by pretreatment with the K ϩ channel inhibitors Ba 2ϩ , 4-aminopyridine, tetraethylammonium chloride, and glibenclamide (12,19). To exclude the possibility that, in our model, VS-1 could affect ionic channels other than the L-type Ca 2ϩ channel, we measured Ca 2ϩ transients on electric-field-stimulated cardiomyocytes.…”

“…VS-1 and VS-2 induce a negative inotropic effect on the isolated heart of the eel (19), frog (11,12,26), and rat (9) under basal conditions and after ␤-adrenergic stimulation. Interestingly, although the action of VSs on frog cardiac muscle appears direct, i.e., independent of endocardial endothelial (EE) cells and muscarinic/␤-adrenergic-related pathways (12,26), in the heart of the eel, it depends on EE-dependent activation of M 1 muscarinic receptors and G i/o , as well as synthesis of nitric oxide (NO) and cGMP (19). Moreover, in eel and frog heart, changes in cytoskeletal dynamics seem to play a crucial role in the negative inotropic effect of VS-1 (22).…”

Chromogranin A Restricts Drug Penetration and Limits the Ability of NGR-TNF to Enhance Chemotherapeutic Efficacy

“…Indeed, in the latter case the tumor vasculature is exposed to much higher levels of CgA (possibly >1 mmol/L) compared with those of nonneuroendocrine tumors, owing to the fact that the source of CgA is the tumor itself. Because the dose-response curves of CgA and VS-1 in various biological assays are "bell shaped" with loss of activity at micromolar concentrations (36,43,44), higher levels of CgA in the tumor microenvironment could be, paradoxically, less active than low levels of circulating CgA. Furthermore, different proteolytic processing may occur to CgA released by neuroendocrine tumor cells and by normal cells (45).…”

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).…”