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Investigation of signaling pathways that mediate the inotropic effect of urotensin-II in human heart

, : Investigation of signaling pathways that mediate the inotropic effect of urotensin-II in human heart. Cardiovascular Research 63(4): 673-681, September 1

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 muM) to desensitize PKC, the PKC inhibitor chelerythrine (10 muM), 10 muM 4alpha-phorbol that does not desensitize PKC, the myosin light chain kinase inhibitor wortmannin (50 nM, 10 muM), or the Rho kinase inhibitor Y-27632 (0.1 - 10 muM). 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 < 0.05, n = 6) and PKCalpha/betaII (1.4 +/- 0.2-fold compared to non-stimulated controls, P < 0.05, n = 7). Pretreatment of tissues with PMA caused a marked reduction in the inotropic effect of hU-II, but did not affect hU-II-mediated phosphorylation of MLC-2. The inotropic response was inhibited by chelerythrine, but not 4alpha-phorbol or wortmannin. Although Y-27632 also reduced the positive inotropic response to hU-II, this was associated with a marked reduction in basal force of contraction. RhoA. GTP was immunoprecipitated in tissues pretreated with or without hU-II, with findings showing no detectable activation of RhoA in the agonist stimulated tissues. Conclusions: The findings indicated that hU-II increased force of contraction in human heart via a PKC-dependent mechanism and increased phosphorylation of MLC-2, although this was independent of PKC. The positive inotropic effect was independent of myosin light chain kinase and RhoA-Rho kinase signaling pathways.

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Muller, H., 1967: Ecological studies on water relations with reference to Vaccinium myrtillus L. Gives figures for the daily total transpiration in two growing seasons (determined by a rapid weighing method) of a cover of V. myrtillus under a 65-year-old Pinus sylvestris stand near Eberswalde, on a sandy podzolized site with a low water table...

Mills, B. J.; Suter, P.; Lake, P. S., 1976: The amount and distribution of calcium in the exoskeleton of inter molt crayfish of the genera engaeus and geocharax. Total Ca concentration and Ca distribution were studied in the exoskeletons of the crayfish Engaeus fossor, E. leptorhynchus, Engaeus sp. and Geocharax falcata. In all species the total exoskeleton Ca concentration was low in comparison with most...

Rumiantsev D.O.; Piotrovskii V.K.; Metelitsa V.I.; Slastnikova I.D.; Martsevich S.Yu; Kokurina E.V., 1989: Serum binding of nifedipine and verapamil in patients with ischemic heart disease on monotherapy. Serum free fractions of nifedipine, verapamil and some of their metabolites were measured in patients with ischaemic heart disease receiving single oral dose and chronic monotherapy and were compared with those obtained in vitro. The percentages o...

Seiden L.S.; Ricaurte G.A., 1987: Neurotoxicity of methamphetamine and related drugs. Meltzer, H Y (Ed ) Psychopharmacology: The Third Generation Of Progress Xliii 1780p +++raven Press: New York, New York, Usa Illus 359-366

Aronow, Wilbert S., 1994: Extracranial carotid arterial disease. Comprehensive Therapy 20(3): 192-197

Aveling T.A.S.; Rijkenberg F.H.J., 1989: Behavior of phytophthora cinnamomi zoospores on roots of four avocado cultivars. Scanning electron microscopy was used to study the behavior of Phytophthora cinnamomi zoospores on the roots of three tolerant avocado cultivars, Duke 7, G6 and Martin Grande, and a susceptible Edranol cultivar. Zoospores were attracted to the reg...

Petrova, Ad; Sizova, Tp; Mirchink, Tg; Pokrovskaia, Iv, 1980: Microscopic soil fungi found in the hills of the termite, Anacanthotermes ahngerianus Jac. in the West Turkmenistan (Isoptera: Hodotermitidae). Mikologiia i fitopatologiia 14(1): 13-20

Ip, Clement; Briggs, Stephanie P.; Haegele, Albert D.; Thompson, Henry J.; Storkson, Jayne; Scimeca, Joseph A., 1996: The efficacy of conjugated linoleic acid in mammary cancer prevention is independent of the level or type of fat in the diet. The objective of the present study was to investigate whether the anticarcinogenic activity of conjugated linoleic acid (CLA) is affected by the amount and composition of dietary fat consumed by the host. Because the anticancer agent of interest i...

Tariq, Bushra; Karan, Sheila, 2000: Congenital methemoglobinemia. A case of congenital methemoglobinemia presenting at birth is reported. The clinical signs, differential diagnosis, pathogenesis and management of this disorder are discussed.

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