Vasoinhibitory activity of synthetic peptides from the amino terminus of chromogranin A.
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.
Angeletti
R H
RH
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461.
Aardal
S
S
Serck-Hanssen
G
G
Gee
P
P
Helle
K B
KB
D000818:Animals; D001011:Aorta; D002417:Cattle; D002460:Cell Line; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D012501:Saphenous Vein; D014661:Vasoconstriction / Q000187:drug effects*
D053379:Chromogranin A; D002864:Chromogranins; D016232:Endothelins; D010446:Peptide Fragments; C067131:chromogranin A (1-40); C064110:vasostatin I