The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its independence of extracellular calcium in isolated segments of human blood vessels.
Endothelium-independent vasoconstrictor responses in isolated segments of human internal thoracic artery (ITA) and saphenous vein (SV) were used as a bioassay system for the vasoinhibitory activity of bovine chromogranin A (CGA). Preincubation with vasostatin (0.8 micrograms/ml), containing the N-terminal domain of CGA, (CGA1-76, CGA1-113 and CGA1-143ff), inhibited the contractile responses evoked by 80 mM K+, 2.6 microM noradrenaline (NA), or 65 nM endothelin-1 (ET-1) in Ca(2+)-free solution in SV but not in ITA. The results demonstrate a vasoinhibitory activity in vasostatin and show that there is a marked difference between the arterial and venous segments in the Ca2+ independent component of the inhibitory response. A vascular role for the N-terminal domain of CGA is indicated, presumably by inhibiting Ca2+ release from intracellular stores in the human vein but not the artery.
Aardal
S
S
Department of Physiology, University of Bergen, Norway.
Helle
K B
KB
D002118:Calcium / Q000378:metabolism; D053379:Chromogranin A; D002864:Chromogranins / 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; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism; D013895:Thoracic Arteries / Q000187:drug effects* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D016232:Endothelins; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine