scholarly journals Failure of dibutyryl and 8-bromo-cyclic gmp to mimic the antagonistic action of carbachol on the positive inotropic effects of sympathomimetic amines in the canine isolated ventricular myocardium

1979 ◽  
Vol 29 (3) ◽  
pp. 423-433 ◽  
Author(s):  
Masaso Endoh ◽  
Tetsuo Shimizu
Keyword(s):  
Cyclic Gmp ◽  
Ventricular Myocardium ◽  
Antagonistic Action ◽  
Inotropic Effects ◽  
Sympathomimetic Amines ◽  
Positive Inotropic Effects

Small concentrations of mercury enhances positive inotropic effects in the rat ventricular myocardium

2005 ◽  
Vol 20 (1) ◽  
pp. 22-25
Author(s):  
Diego Falcochio ◽  
Gabriela Poltronieri Souza de Assis ◽  
Ivanita Stefanon ◽  
Dalton Valentim Vassallo
Keyword(s):  
Ventricular Myocardium ◽  
Inotropic Effects ◽  
Positive Inotropic Effects

Atrial myocardium is the predominant inotropic target of adrenomedullin in the human heart

2007 ◽  
Vol 293 (5) ◽  
pp. H3001-H3007 ◽  
Author(s):  
Egbert Bisping ◽  
Gero Tenderich ◽  
Paul Barckhausen ◽  
Burkhard Stumme ◽  
Sebastian Bruns ◽  
...  
Keyword(s):  
Light Emission ◽  
Ventricular Myocardium ◽  
Right Atrial ◽  
Dependent Manner ◽  
Atrial Myocardium ◽  
Concentration Dependent Manner ◽  
Maximal Increase ◽  
Inotropic Effects ◽  
Positive Inotropic Effects ◽  
Camp Levels

Adrenomedullin (ADM) is an endogenous peptide with favorable hemodynamic effects in vivo. In this study, we characterized the direct functional effects of ADM in isolated preparations from human atria and ventricles. In electrically stimulated human nonfailing right atrial trabeculae, ADM (0.0001–1 μmol/l) increased force of contraction in a concentration-dependent manner, with a maximal increase by 35 ± 8% (at 1 μmol/l; P < 0.05). The positive inotropic effect was accompanied by a disproportionate increase in calcium transients assessed by aequorin light emission [by 76 ± 20%; force/light ratio (ΔF/ΔL) 0.58 ± 0.15]. In contrast, elevation of extracellular calcium (from 2.5 to 3.2 mmol/l) proportionally increased force and aequorin light emission (ΔF/ΔL 1.0 ± 0.1; P < 0.05 vs. ADM). Consistent with a cAMP-dependent mechanism, ADM (1 μmol/l) increased atrial cAMP levels by 90 ± 12%, and its inotropic effects could be blocked by the protein kinase A (PKA) inhibitor H-89. ADM also exerted positive inotropic effects in failing atrial myocardium and in nonfailing and failing ventricular myocardium. The inotropic response was significantly weaker in ventricular vs. atrial myocardium and in failing vs. nonfailing myocardium. In conclusion, ADM exerts Ca2+-dependent positive inotropic effects in human atrial and less-pronounced effects in ventricular myocardium. The inotropic effects are related to increased cAMP levels and stimulation of PKA. In heart failure, the responsiveness to ADM is reduced in atria and ventricles.

scholarly journals The insulin- and glucagon-stimulated ‘dense-vesicle’ high-affinity cyclic AMP phosphodiesterase from rat liver. Purification, characterization and inhibitor sensitivity

1987 ◽  
Vol 242 (1) ◽  
pp. 33-42 ◽  
Author(s):  
N J Pyne ◽  
M E Cooper ◽  
M D Houslay
Keyword(s):  
Cyclic Amp ◽  
Rat Liver ◽  
Cyclic Gmp ◽  
Sodium Cholate ◽  
Hill Coefficient ◽  
Major Band ◽  
Inotropic Effects ◽  
Cyclic Amp Phosphodiesterase ◽  
Apparent Homogeneity ◽  
Positive Inotropic Effects

The hormone-stimulated ‘dense-vesicle’ cyclic AMP phosphodiesterase was solubilized as a proteolytically ‘clipped’ species, and purified to apparent homogeneity from rat liver with a 2000-3000-fold purification and a 13-18% yield. It appeared to be a dimer (Mr 112,000), of two Mr-57,000 subunits. Solubilization of either a liver or a hepatocyte membrane fraction, with sodium cholate in the presence of the protein inhibitor benzamidine, identified three protein bands which could be immunoprecipitated by a polyclonal antibody raised against the pure enzyme. The major band at Mr 62,000 is suggested to be the native ‘dense-vesicle’ enzyme, having a Mr-5000 extension which serves to anchor this enzyme to the membrane and which is cleaved off during proteolytic solubilization; the Mr-200,000 band is an aggregate of the Mr-62,000 species, and the Mr-63,000 species is possibly a precursor. The purified ‘clipped’ enzyme hydrolysed cyclic AMP with kinetics indicative of apparent negative co-operativity, with a Hill coefficient (h) of 0.43 and limiting kinetic constants of Km1 = 0.3 +/- 0.05 microM, Km2 = 29 +/- 6 microM, Vmax.1 = 0.114 +/- 0.015 unit/mg of protein and Vmax.2 = 0.633 +/- 0.054 unit/mg of protein. It hydrolysed cyclic GMP with Michaelis kinetics, Km = 10 +/- 1 microM and Vmax. = 4.1 +/- 0.2 units/mg of protein. Cyclic GMP was a potent inhibitor of cyclic AMP hydrolysis, with an IC50 (concn. giving 50% inhibition) of 0.20 +/- 0.01 microM-cyclic GMP when assayed at 0.1 microM-cyclic AMP. This enzyme was inhibited potently by several drugs known to exert positive inotropic effects on the heart, was extremely thermolabile, with a half-life of 4.5 +/- 0.5 min at 40 degrees C, and was shown to be distinct from the rat liver insulin-stimulated peripheral-plasma-membrane cyclic AMP phosphodiesterase [Marchmont, Ayad & Houslay (1981) Biochem. J. 195, 645-652].

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