Vasostatins, Comprising the N‐terminal Domain of Chromogranin A, Suppress Tension in Isolated Human Blood Vessel Segments

Abstract

Chromogranin A (CGA) belongs to a family of highly acidic proteins which are co-stored and co-released with the catecholamines from the mammalian adrenal gland and occur in nmolar concentrations in the human circulation. A vascular function for the adrenomedullary released and circulating CGA has yet to be established. The present study reports on the novel vasoinhibitory effect of the N-terminal domain of the adrenomedullary CGA in isolated segments of the human internal thoracic artery (ITA) and saphenous vein (SV). The collective term vasostatin(s) refers to N-terminal fragments (CGA1-76 and CGA1-113) of apparent molecular weights 7 to 22 kD, to indicate their vascular inhibitory effects. The sustained contractions evoked by the potent vasoconstrictor peptide, endothelin-1 (ET-1) were suppressed when ITA and SV segments were preincubated for 15 min with vasostatins (72 nM). The vasoinhibitory effects were not dependent on an intact endothelium and suppression of the response to 35 nM ET-1 was approximately 77% and approximately 40% in endothelium-denuded ITA and SV segments, respectively. In endothelium-denuded SV segments the vasostatins suppressed the maximal sustained tension response but not the potency for ET-1, indicating that the vasostatin effect did not involve interference with ET-1 binding to its vascular receptor. Preincubation of endothelium-denuded SV segments with nifedipine (1 microM) inhibited the sustained response to ET-1 > or = 10 nM by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterisation of N-terminal chromogranin A and chromogranin B in mammals by region-specific radioimmunoassays and chromatographic separation methods

“…SDS-PAGE electrophoresis was carried out on 16% acrylamide gels. The proteins were immunoblotted to nitrocellulose papers and the immunoreactive components were stained with the bCgA antibodies using the alkaline phosphatase reaction as previously described (Aardal et al 1993). Traces of the N-terminal sequence of the soluble DBH (Skotland & Ljones 1979) were not detected by these analyses and the protein failed to immunostain with a polyclonal antibody to bovine DBH (a kind gift from Dr D Aunis, Strasbourg, France).…”

“…N-terminal amino acid sequence and total amino acid analyses were carried out on the protein dissolved in aqueous 0·1% trifluoroacetic acid. An N-terminal sequence corresponding to CgA1-19 was verified by amino acid analysis and the total amino acid composition corresponded to the intact bCgA (Aardal et al 1993). SDS-PAGE electrophoresis was carried out on 16% acrylamide gels.…”

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

“…In humans, it colocalizes with brain natriuretic peptide (BNP) in ventricular myocytes of the dilated and hypertrophic heart (Pieroni et al, 2007). In addition to its crucial role in secretory vesicle biogenesis (Courel et al, 2006), CgA acts as a prohormone that generates several biologically active peptides, including the dysglycemic hormone pancreastatin (Tatemoto et al, 1986), the vasodilator vasostatin 1 (VS-1) (Aardal et al, 1993), the antimicrobial agent chromacin (Strub et al, 1996) and the catecholamine release-inhibitory peptide catestatin (Mahata et al, 1997;Mahata et al, 2003;Mahata et al, 2004).…”

Chromogranin A Regulates Renal Function by Triggering Weibel–Palade Body Exocytosis

“…23,24 Synthetic CHGA 1-40 spans the very hydrophobic disulfide-bounded domain of the molecule: 25 including effects on the endothelium. 26 In this study, CHGA reproduced the novel endothelial function of triggering EDN1 secretion, 6 whereas other fragments of CHGA, such as pancreastatin (CHGA 273-301 ) and catestatin (CHGA 352-372 ) did not show this action.…”