| Investigation of signaling pathways that mediate the inotropic effect of urotensin-II in human heart (2004) | |||||||||||||
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| Objective: This study investigated signaling pathways that may contribute to the potent positive inotropic effect of human urotensin-II (hU-II) in human isolated right atrial trabeculae obtained from patients with coronary artery disease. Methods: Trabeculae were set up in tissue baths and stimulated to contract at 1 Hz. Tissues were incubated with 20 nM hU-II with or without phorbol 12-myristate 13-acetate (PMA, 10 µM) to desensitize PKC, the PKC inhibitor chelerythrine (10 µM), 10 µM 4-phorbol that does not desensitize PKC, the myosin light chain kinase inhibitor wortmannin (50 nM, 10 µM), or the Rho kinase inhibitor Y-27632 (0.1–10 µM). Activated RhoA was determined by affinity immunoprecipitation, and phosphorylation of signaling proteins was determined by SDS-PAGE. Results: hU-II caused a potent positive inotropic response in atrial trabeculae, and this was concomitant with increased phosphorylation of regulatory myosin light chain (MLC-2, 1.8±0.4-fold, P | |||||||||||||
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