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

Abstract

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.