Vasoinhibitory activity of synthetic peptides from the amino terminus of chromogranin A

• Published in: Acta physiologica Scandinavica Vol. 152; no. 1; p. 11
• Main Authors: Angeletti, R H, Aardal, S, Serck-Hanssen, G, Gee, P, Helle, K B
• Format: Journal Article
• Language: English
• Published: England 01.09.1994
• Subjects: Animals; Aorta; Cattle; Cell Line; Chromogranin A; Chromogranins - metabolism; Chromogranins - pharmacology; Endothelins - pharmacology; Humans; In Vitro Techniques; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Saphenous Vein; Vasoconstriction - drug effects
• ISSN: 0001-6772
• DOI: 10.1111/j.1748-1716.1994.tb09780.x

Naturally occurring amino terminal fragments of chromogranin A (CGA), the calcium-binding protein found in all endocrine secretory vesicles, have vasoinhibitory activity when tested in isolated segments of the endothelium-denuded human saphenous vein. Synthetic peptides corresponding to sequences within the first 76 residues of chromogranin A have been made and tested for biological activity. Full length vasostatin I (CGA1-76) (40 nM), but not the truncated vasostatin I, CGA1-40 (100 nM) mimics natural chromogranin A fragments in its inhibition of contractions induced by endothelin-1 (ET-1) in calcium containing medium. CGA1-40 (100 nM) mimics the inhibitory effect of the vasostatins on the contractions induced in the absence of extracellular calcium by high potassium and noradrenaline, but not by ET-1. The iodinated peptides both exhibit saturable binding in an aortic smooth muscle cell line, indicative of a single class of high affinity binding protein ('receptor' with an apparent KD of approximately 45 nM. This binding is not affected by endothelin-1. Iodinated peptides can be crosslinked to a single polypeptide in binding experiments performed on intact calf aortic smooth muscle cells.