Thrombin stimulates the simultaneous release of endothelin-1 and big endothelin-1 from cultured porcine endothelial cells via a mechanism likely involving intracellular Ca2+ mobilization and PKC activation.
Does thrombin stimulate the release of endothelin-1 and big endothelin-1 in cultured porcine endothelial cells via PKC activation and Ca2+ mobilization?
Thrombin stimulates the simultaneous release of endothelin-1 and big endothelin-1 from endothelial cells through mechanisms involving protein kinase C and calcium mobilization.
Cultured porcine endothelial cells (EC) released immunoreactive endothelin-1 (ir-endothelin-1) and big endothelin-1 (ir-big endothelin-1) into the medium in a time-dependent way. Reverse-phase high-pressure liquid chromatography coupled with radioimmunoassay showed that the major component of ir-endothelin-1 corresponded to standard endothelin-1 (1-21) and that the major component of ir-big endothelin-1 corresponded to standard big endothelin-1 (porcine 1-39). This release was strongly inhibited by cycloheximide and was, therefore, related to de novo protein synthesis. The release of greater amounts was stimulated by thrombin. The protein kinase C (PKC) inhibitors from two chemical classes, H7 and staurosporine, inhibited release following such stimulation in a relatively dose-dependent way. Neither H7 nor staurosporine affected the basal release of both endothelin-1 and big endothelin-1. Phorbol myristate acetate, which activates PKC and the Ca2+ ionophore A23187, stimulated the release of ir-endothelin-1 and ir-big endothelin-1 in a dose-dependent way, respectively. In addition, the combination of both compounds had a synergistic effect. An inactive enantiomer of phorbol ester, 4 alpha-phorbol-12,13-didecanoate had no effect on the release of ir-endothelin-1 and ir-big endothelin-1. These results suggest that cultured EC release endothelin-1 and big endothelin-1 simultaneously, and that thrombin stimulates this release by a mechanism that probably involves intracellular Ca2+ mobilization and the activation of PKC.
Kohno et al. (Tue,) reported a other. Thrombin vs. Basal release was evaluated on Release of immunoreactive endothelin-1 and big endothelin-1. Thrombin stimulates the simultaneous release of endothelin-1 and big endothelin-1 from cultured porcine endothelial cells via a mechanism likely involving intracellular Ca2+ mobilization and PKC activation.
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