The Experts below are selected from a list of 66 Experts worldwide ranked by ideXlab platform
E G Krause - One of the best experts on this subject based on the ideXlab platform.
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activation of β2 adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban troponin i and c protein in ventricular myocardium from patients with terminal heart failure
Circulation, 1999Co-Authors: A J Kaumann, Louise Sanders, Sabine Bartel, Peter Karczewski, Peter C M Molenaar, Kylie Burrell, Donathe Vetter, Petra Hempel, E G KrauseAbstract:Background—Catecholamines hasten cardiac relaxation through β-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of β1- and β2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results—Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 μmol/L) or Zinterol (10 μmol/L), mediated through β2-adrenergic receptors, and of norepinephrine (10 μmol/L), mediated through β1-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinep...
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β2 adrenoceptor activation by Zinterol causes protein phosphorylation contractile effects and relaxant effects through a camp pathway in human atrium
Molecular and Cellular Biochemistry, 1996Co-Authors: Alberto J Kaumann, Louise Sanders, James A Lynham, Sabine Bartel, Meike Kuschel, Peter Karczewski, E G KrauseAbstract:Evidence from ventricular preparations of cat, sheep, rat and dog suggests that both β1-adrenoceptors (β1AR) and β2-adrenoceptors (β2AR) mediate positive inotropic effects but that only β1AR do it through activation of a cAMP pathway. On the other hand, our evidence has shown that both β1AR and β2AR hasten relaxation of isolated human myocardium consistent with a common cAMP pathway. We have now investigated in the isolated human right atrial appendage, a tissue whose β-AR comprise around 2/3 of β1AR and 1/3 of β2AR, whether or not β2AR-mediated effects occur via activation of a cAMP pathway. We carried out experiments on atria obtained from patients without advanced heart failure undergoing open heart surgery. To activate β2AR, we used the β2AR-selective ligand Zinterol. Experiments were carried out on paced atrial strips (1 Hz) and tissue homogenates and membrane particles. Zinterol caused positive inotropic and lusitropic (i.e. reduction of t1/2 of relaxation) effects with EC50 values of 3 and 2 nM, respectively. The Zinterol-evoked effects were unaffected by the β1AR-selective antagonist CGP 20712A (300 nM) but blocked surmountably by the β2AR-selective antagonist ICI 118551 (50 nM) which reduced both EC50 values to 1 µM. Zinterol stimulated adenylyl cyclase activity with an EC50 of 30 nM and intrinsic activity of 0.75 with respect to (—)-isoprenaline (600 µM); the effects were resistant to blockade by CGP 20712A (300 nM) but antagonised surmountably by ICI 118551 (50 nM). Zinterol bound to membrane βAR labelled with (—)-[125I] cyanopindolol with higher affinity for β2AR than for β1AR; the binding to β2AR but not to β1AR was reduced by GTPγS (10 µM). In the presence of CGP 20712A (300 nM) (—)-isoprenaline (400 µM) (to activate both β1AR and β2AR maximally) and Zinterol (10 µM) increased contractile force 3.4-fold and 2.5-fold respectively and reduced relaxation t1/2 by 32% and 18% respectively. These effects of (—)-isoprenaline and Zinterol were associated (5 min incubation) with phosphorylation (pmol P/mg supernatant protein) of troponin I and C-protein to values of 8.4 ± 2.0 vs 12.4 ± 2.3 and 10.1 ± 2.5 vs 8.6 ± 1.6 respectively. (—)-Isoprenaline and Zinterol also caused phosphorylation of phospholamban (1.8 ± 0.3 vs 0.4 ± 0.1 pmol P/mg respectively) specifically at serine residues. We conclude that in human atrial myocardium activation of both β1AR and β2AR leads to cAMP-dependent phosphorylation of proteins involved in augmenting both contractility and relaxation.
Peter C M Molenaar - One of the best experts on this subject based on the ideXlab platform.
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murine ventricular l type ca 2 current is enhanced by Zinterol via beta 1 adrenoceptors and is reduced in tg4 mice overexpressing the human beta 2 adrenoceptor
British Journal of Pharmacology, 2001Co-Authors: Jurgen F Heubach, Eva M Graf, Peter C M Molenaar, Andreas Jager, Frank Schroder, Stefan Herzig, Sian E Harding, Ursula RavensAbstract:1 The functional coupling of B-2-adrenoceptors (beta (2)-ARs) to murine L-type Ca2+ current (I-Ca(L)) was investigated with two different approaches. The beta (2)-AR signalling cascade was activated either with the beta (2)-AR selective agonist Zinterol (myocytes from wild-type mice), or by spontaneously active, unoccupied beta (2)-ARs (myocytes from TG4 mice with 435 fold overexpression of human beta (2)-ARs). Ca2+ and Ba2+ currents were recorded in the whole-cell and cell-attached configuration of the patch- clamp technique, respectively. 2 Zinterol (10 muM) significantly increased I-Ca(L) amplitude of wild-type myocytes by 19+/-5%, and this effect was markedly enhanced after inactivation of Gi-proteins with pertussis-toxin (PTX; 76+/-13% increase). However, the effect of Zinterol was entirely mediated by the beta (1)-AR subtype, since it was blocked by the beta (1)-AR selective antagonist CGP 20712A (300 nM). The beta (2)-AR selective antagonist ICI 118,551 (50 nM) did not affect the response of I-Ca(L) to Zinterol. 3 In myocytes with beta (2)-AR overexpression I-Ca(L) was not stimulated by the activated signalling cascade. On the contrary, I-Ca(L) was lower in TG4 myocytes and a significant reduction of single-channel activity was identified as a reason for the lower whole-cell I-Ca(L). The beta (2)-AR inverse agonist ICI 118,551 did not further decrease I-Ca(L). PTX-treatment increased current amplitude to values found in control myocytes. 4 In conclusion, there is no evidence for beta (2)-AR mediated increases of I-Ca(L) in wild-type mouse ventricular myocytes. Inactivation of Gi-proteins does not unmask beta (2)-AR responses to Zinterol, but augments beta (1)-AR mediated increases of I-Ca(L). In the mouse model of beta (2)-AR overexpression I-Ca(L) is reduced due to tonic activation of Gi-proteins.
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activation of β2 adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban troponin i and c protein in ventricular myocardium from patients with terminal heart failure
Circulation, 1999Co-Authors: A J Kaumann, Louise Sanders, Sabine Bartel, Peter Karczewski, Peter C M Molenaar, Kylie Burrell, Donathe Vetter, Petra Hempel, E G KrauseAbstract:Background—Catecholamines hasten cardiac relaxation through β-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of β1- and β2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results—Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 μmol/L) or Zinterol (10 μmol/L), mediated through β2-adrenergic receptors, and of norepinephrine (10 μmol/L), mediated through β1-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinep...
Peter Karczewski - One of the best experts on this subject based on the ideXlab platform.
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activation of β2 adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban troponin i and c protein in ventricular myocardium from patients with terminal heart failure
Circulation, 1999Co-Authors: A J Kaumann, Louise Sanders, Sabine Bartel, Peter Karczewski, Peter C M Molenaar, Kylie Burrell, Donathe Vetter, Petra Hempel, E G KrauseAbstract:Background—Catecholamines hasten cardiac relaxation through β-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of β1- and β2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results—Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 μmol/L) or Zinterol (10 μmol/L), mediated through β2-adrenergic receptors, and of norepinephrine (10 μmol/L), mediated through β1-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinep...
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β2 adrenoceptor activation by Zinterol causes protein phosphorylation contractile effects and relaxant effects through a camp pathway in human atrium
Molecular and Cellular Biochemistry, 1996Co-Authors: Alberto J Kaumann, Louise Sanders, James A Lynham, Sabine Bartel, Meike Kuschel, Peter Karczewski, E G KrauseAbstract:Evidence from ventricular preparations of cat, sheep, rat and dog suggests that both β1-adrenoceptors (β1AR) and β2-adrenoceptors (β2AR) mediate positive inotropic effects but that only β1AR do it through activation of a cAMP pathway. On the other hand, our evidence has shown that both β1AR and β2AR hasten relaxation of isolated human myocardium consistent with a common cAMP pathway. We have now investigated in the isolated human right atrial appendage, a tissue whose β-AR comprise around 2/3 of β1AR and 1/3 of β2AR, whether or not β2AR-mediated effects occur via activation of a cAMP pathway. We carried out experiments on atria obtained from patients without advanced heart failure undergoing open heart surgery. To activate β2AR, we used the β2AR-selective ligand Zinterol. Experiments were carried out on paced atrial strips (1 Hz) and tissue homogenates and membrane particles. Zinterol caused positive inotropic and lusitropic (i.e. reduction of t1/2 of relaxation) effects with EC50 values of 3 and 2 nM, respectively. The Zinterol-evoked effects were unaffected by the β1AR-selective antagonist CGP 20712A (300 nM) but blocked surmountably by the β2AR-selective antagonist ICI 118551 (50 nM) which reduced both EC50 values to 1 µM. Zinterol stimulated adenylyl cyclase activity with an EC50 of 30 nM and intrinsic activity of 0.75 with respect to (—)-isoprenaline (600 µM); the effects were resistant to blockade by CGP 20712A (300 nM) but antagonised surmountably by ICI 118551 (50 nM). Zinterol bound to membrane βAR labelled with (—)-[125I] cyanopindolol with higher affinity for β2AR than for β1AR; the binding to β2AR but not to β1AR was reduced by GTPγS (10 µM). In the presence of CGP 20712A (300 nM) (—)-isoprenaline (400 µM) (to activate both β1AR and β2AR maximally) and Zinterol (10 µM) increased contractile force 3.4-fold and 2.5-fold respectively and reduced relaxation t1/2 by 32% and 18% respectively. These effects of (—)-isoprenaline and Zinterol were associated (5 min incubation) with phosphorylation (pmol P/mg supernatant protein) of troponin I and C-protein to values of 8.4 ± 2.0 vs 12.4 ± 2.3 and 10.1 ± 2.5 vs 8.6 ± 1.6 respectively. (—)-Isoprenaline and Zinterol also caused phosphorylation of phospholamban (1.8 ± 0.3 vs 0.4 ± 0.1 pmol P/mg respectively) specifically at serine residues. We conclude that in human atrial myocardium activation of both β1AR and β2AR leads to cAMP-dependent phosphorylation of proteins involved in augmenting both contractility and relaxation.
Sabine Bartel - One of the best experts on this subject based on the ideXlab platform.
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activation of β2 adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban troponin i and c protein in ventricular myocardium from patients with terminal heart failure
Circulation, 1999Co-Authors: A J Kaumann, Louise Sanders, Sabine Bartel, Peter Karczewski, Peter C M Molenaar, Kylie Burrell, Donathe Vetter, Petra Hempel, E G KrauseAbstract:Background—Catecholamines hasten cardiac relaxation through β-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of β1- and β2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results—Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 μmol/L) or Zinterol (10 μmol/L), mediated through β2-adrenergic receptors, and of norepinephrine (10 μmol/L), mediated through β1-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinep...
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β2 adrenoceptor activation by Zinterol causes protein phosphorylation contractile effects and relaxant effects through a camp pathway in human atrium
Molecular and Cellular Biochemistry, 1996Co-Authors: Alberto J Kaumann, Louise Sanders, James A Lynham, Sabine Bartel, Meike Kuschel, Peter Karczewski, E G KrauseAbstract:Evidence from ventricular preparations of cat, sheep, rat and dog suggests that both β1-adrenoceptors (β1AR) and β2-adrenoceptors (β2AR) mediate positive inotropic effects but that only β1AR do it through activation of a cAMP pathway. On the other hand, our evidence has shown that both β1AR and β2AR hasten relaxation of isolated human myocardium consistent with a common cAMP pathway. We have now investigated in the isolated human right atrial appendage, a tissue whose β-AR comprise around 2/3 of β1AR and 1/3 of β2AR, whether or not β2AR-mediated effects occur via activation of a cAMP pathway. We carried out experiments on atria obtained from patients without advanced heart failure undergoing open heart surgery. To activate β2AR, we used the β2AR-selective ligand Zinterol. Experiments were carried out on paced atrial strips (1 Hz) and tissue homogenates and membrane particles. Zinterol caused positive inotropic and lusitropic (i.e. reduction of t1/2 of relaxation) effects with EC50 values of 3 and 2 nM, respectively. The Zinterol-evoked effects were unaffected by the β1AR-selective antagonist CGP 20712A (300 nM) but blocked surmountably by the β2AR-selective antagonist ICI 118551 (50 nM) which reduced both EC50 values to 1 µM. Zinterol stimulated adenylyl cyclase activity with an EC50 of 30 nM and intrinsic activity of 0.75 with respect to (—)-isoprenaline (600 µM); the effects were resistant to blockade by CGP 20712A (300 nM) but antagonised surmountably by ICI 118551 (50 nM). Zinterol bound to membrane βAR labelled with (—)-[125I] cyanopindolol with higher affinity for β2AR than for β1AR; the binding to β2AR but not to β1AR was reduced by GTPγS (10 µM). In the presence of CGP 20712A (300 nM) (—)-isoprenaline (400 µM) (to activate both β1AR and β2AR maximally) and Zinterol (10 µM) increased contractile force 3.4-fold and 2.5-fold respectively and reduced relaxation t1/2 by 32% and 18% respectively. These effects of (—)-isoprenaline and Zinterol were associated (5 min incubation) with phosphorylation (pmol P/mg supernatant protein) of troponin I and C-protein to values of 8.4 ± 2.0 vs 12.4 ± 2.3 and 10.1 ± 2.5 vs 8.6 ± 1.6 respectively. (—)-Isoprenaline and Zinterol also caused phosphorylation of phospholamban (1.8 ± 0.3 vs 0.4 ± 0.1 pmol P/mg respectively) specifically at serine residues. We conclude that in human atrial myocardium activation of both β1AR and β2AR leads to cAMP-dependent phosphorylation of proteins involved in augmenting both contractility and relaxation.
Louise Sanders - One of the best experts on this subject based on the ideXlab platform.
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activation of β2 adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban troponin i and c protein in ventricular myocardium from patients with terminal heart failure
Circulation, 1999Co-Authors: A J Kaumann, Louise Sanders, Sabine Bartel, Peter Karczewski, Peter C M Molenaar, Kylie Burrell, Donathe Vetter, Petra Hempel, E G KrauseAbstract:Background—Catecholamines hasten cardiac relaxation through β-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of β1- and β2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results—Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 μmol/L) or Zinterol (10 μmol/L), mediated through β2-adrenergic receptors, and of norepinephrine (10 μmol/L), mediated through β1-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinep...
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β2 adrenoceptor activation by Zinterol causes protein phosphorylation contractile effects and relaxant effects through a camp pathway in human atrium
Molecular and Cellular Biochemistry, 1996Co-Authors: Alberto J Kaumann, Louise Sanders, James A Lynham, Sabine Bartel, Meike Kuschel, Peter Karczewski, E G KrauseAbstract:Evidence from ventricular preparations of cat, sheep, rat and dog suggests that both β1-adrenoceptors (β1AR) and β2-adrenoceptors (β2AR) mediate positive inotropic effects but that only β1AR do it through activation of a cAMP pathway. On the other hand, our evidence has shown that both β1AR and β2AR hasten relaxation of isolated human myocardium consistent with a common cAMP pathway. We have now investigated in the isolated human right atrial appendage, a tissue whose β-AR comprise around 2/3 of β1AR and 1/3 of β2AR, whether or not β2AR-mediated effects occur via activation of a cAMP pathway. We carried out experiments on atria obtained from patients without advanced heart failure undergoing open heart surgery. To activate β2AR, we used the β2AR-selective ligand Zinterol. Experiments were carried out on paced atrial strips (1 Hz) and tissue homogenates and membrane particles. Zinterol caused positive inotropic and lusitropic (i.e. reduction of t1/2 of relaxation) effects with EC50 values of 3 and 2 nM, respectively. The Zinterol-evoked effects were unaffected by the β1AR-selective antagonist CGP 20712A (300 nM) but blocked surmountably by the β2AR-selective antagonist ICI 118551 (50 nM) which reduced both EC50 values to 1 µM. Zinterol stimulated adenylyl cyclase activity with an EC50 of 30 nM and intrinsic activity of 0.75 with respect to (—)-isoprenaline (600 µM); the effects were resistant to blockade by CGP 20712A (300 nM) but antagonised surmountably by ICI 118551 (50 nM). Zinterol bound to membrane βAR labelled with (—)-[125I] cyanopindolol with higher affinity for β2AR than for β1AR; the binding to β2AR but not to β1AR was reduced by GTPγS (10 µM). In the presence of CGP 20712A (300 nM) (—)-isoprenaline (400 µM) (to activate both β1AR and β2AR maximally) and Zinterol (10 µM) increased contractile force 3.4-fold and 2.5-fold respectively and reduced relaxation t1/2 by 32% and 18% respectively. These effects of (—)-isoprenaline and Zinterol were associated (5 min incubation) with phosphorylation (pmol P/mg supernatant protein) of troponin I and C-protein to values of 8.4 ± 2.0 vs 12.4 ± 2.3 and 10.1 ± 2.5 vs 8.6 ± 1.6 respectively. (—)-Isoprenaline and Zinterol also caused phosphorylation of phospholamban (1.8 ± 0.3 vs 0.4 ± 0.1 pmol P/mg respectively) specifically at serine residues. We conclude that in human atrial myocardium activation of both β1AR and β2AR leads to cAMP-dependent phosphorylation of proteins involved in augmenting both contractility and relaxation.
