Cilostamide potentiates more the positive inotropic effects of (−)-adrenaline through β2-adrenoceptors than the effects of (−)-noradrenaline through β1-adrenoceptors in human atrial myocardium

@article{Christ2006CilostamidePM,
  title={Cilostamide potentiates more the positive inotropic effects of (−)-adrenaline through $\beta$2-adrenoceptors than the effects of (−)-noradrenaline through $\beta$1-adrenoceptors in human atrial myocardium},
  author={Torsten Christ and Andreas Engel and Ursula Ravens and Alberto Julio Kaumann},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  year={2006},
  volume={374},
  pages={249-253}
}
  • T. ChristA. Engel A. Kaumann
  • Published 15 November 2006
  • Biology, Medicine, Chemistry
  • Naunyn-Schmiedeberg's Archives of Pharmacology
Activation of both β1- and β2-adrenoceptors increases the contractility of human atrial myocardium through cyclic AMP-dependent pathways. Cyclic AMP is hydrolised by phosphodiesterases, but little is known about which isoenzymes catalyse inotropically relevant cyclic AMP accumulated upon stimulation of β-adrenoceptor subtypes. We have compared the positive inotropic effects of (−)-noradrenaline and (−)-adrenaline, mediated through β1- and β2-adrenoceptors, respectively, in the absence and… 

(-)-Adrenaline elicits positive inotropic, lusitropic, and biochemical effects through β2-adrenoceptors in human atrial myocardium from nonfailing and failing hearts, consistent with Gs coupling but not with Gi coupling

The hastening of relaxation caused by (-)-adrenaline together with the PKA-catalyzed phosphorylation of the three proteins involved in relaxation, indicate coupling of β2-adrenoceptors to Gs protein.

The effects of both noradrenaline and CGP12177, mediated through human β1-adrenoceptors, are reduced by PDE3 in human atrium but PDE4 in CHO cells

The role of PDE3 and PDE4 on signals through the H and L sites in human myocardium was sought to unravel and cilostamide, but not rolipram, increased the positive inotropic effects and abolished the time dependent fade of both agonists.

Phosphodiesterases PDE3 and PDE4 jointly control the inotropic effects but not chronotropic effects of (−)-CGP12177 despite PDE4-evoked sinoatrial bradycardia in rat atrium

These isoenzymes jointly reduce (−)-CGP12177-evoked increases of left atrial contractility through β1LAR and Cyclic AMP appears to maintain sinoatrial rate and PDE4 elicits bradycardia through hydrolysis of cAMP in a compartment distinct from the β1-adrenoceptor-induced cAMP compartment through which cAMP causes tachycardia.

AkrinorTM, a Cafedrine/ Theodrenaline Mixture (20:1), Increases Force of Contraction of Human Atrial Myocardium But Does Not Constrict Internal Mammary Artery In Vitro

AkinorTM increased cardiac contractile force by direct sympathomimetic actions and PDE inhibition, did not constrict A. mammaria interna rings, but shifted the noradrenaline curve rightward from -logEC50 6.18 ±0.08 to 5.23 ± 0.05 M.mam maria rings, compatible with an α-AR antagonistic effect or PDE inhibited.

HUMAN HEART β‐ADRENOCEPTORS: β1‐ADRENOCEPTOR DIVERSIFICATION THROUGH ‘AFFINITY STATES’ AND POLYMORPHISM

Investigation of the effect of long‐term maximally tolerated carvedilol administration on left ventricular ejection fraction (LVEF) in patients with non‐ischaemic cardiomyopathy and segregation of patients into Arg389Gly‐β1‐adrenoceptors found that carveilol caused a greater increase in left vent cardiac ejection faction in patients carrying the Arg389 allele.

Atropine augments cardiac contractility by inhibiting cAMP-specific phosphodiesterase type 4

It is proposed that inhibition of PDE4 by atropine accounts, at least in part, for the induction of tachycardia and the arrhythmogenic potency of this drug.

PDE4 in the human heart – major player or little helper?

The key result is that the PDE4 inhibitor rolipram does not affect the positive inotropic effects of β1‐ or β2‐adrenoceptor stimulation, which is an important and reassuring finding.

Phosphodiesterase-4 activity: a critical modulator of atrial contractility and arrhythmogenesis.

  • David R Van WagonerBruce D Lindsay
  • Biology, Medicine
    Journal of the American College of Cardiology
  • 2012

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