Human chromostatin inhibits endothelin-1-induced contractures in human blood vessels.
Isolated endothelium-denuded segments of the human internal thoracic artery (ITA) and saphenous vein (SV) have been used for characterization of vasoinhibitory effects of the chromostatin (hChs) sequence of human chromogranin A (CGA124-143). In SV preincubation with hChs inhibited the response to depolarizing high K+ in Ca(2+)-free medium in a concentration dependent manner (EC50 approximately 2 nM). At 200 nM hChs the tension response to high K+ (80 mM) was inhibited by 44% (n = 8) and the tension response to noradrenaline (2.6 microM) was inhibited by 20% (n = 6), but the tension response to endothelin-1 (65 nM) (ET-1) was not affected. In ITA no effect of hChs was observed on tension response to K+ or ET-1 in Ca(2+)-free medium. On the other hand, in Ca(2+)-containing medium the tension evoked by 65 nM ET-1 was no longer sustained in segments preincubated with 200 nM hChs and declined spontaneously to 76 +/- 12% (n = 6) of maximal tension after 6 min. A vascular function for the Chs sequence of the human CGA is thus indicated, inhibiting different components of vasoconstrictor responses in the human SV and ITA segments.
Aardal
S
S
Department of Physiology, P.K.I. University of Bergen, Norway.
Galindo
E
E
Aunis
D
D
Helle
K B
KB
D002118:Calcium / Q000378:metabolism; D053379:Chromogranin A; D002864:Chromogranins / Q000502:physiology*; D016232:Endothelins / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D012501:Saphenous Vein; D013895:Thoracic Arteries
D053379:Chromogranin A; D002864:Chromogranins; D016232:Endothelins; D010446:Peptide Fragments; C067412:chromostatin; D002118:Calcium