These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Inotropy and L-type Ca2+ current, activated by beta1- and beta2-adrenoceptors, are differently controlled by phosphodiesterases 3 and 4 in rat heart.
    Author: Christ T, Galindo-Tovar A, Thoms M, Ravens U, Kaumann AJ.
    Journal: Br J Pharmacol; 2009 Jan; 156(1):62-83. PubMed ID: 19133992.
    Abstract:
    BACKGROUND AND PURPOSE: beta(1)- and beta(2)-adrenoceptors coexist in rat heart but beta(2)-adrenoceptor-mediated inotropic effects are hardly detectable, possibly due to phosphodiesterase (PDE) activity. We investigated the influence of the PDE3 inhibitor cilostamide (300 nmol x L(-1)) and the PDE4 inhibitor rolipram (1 micromol x L(-1)) on the effects of (-)-catecholamines. EXPERIMENTAL APPROACH: Cardiostimulation evoked by (-)-noradrenaline (ICI118551 present) and (-)-adrenaline (CGP20712A present) through beta(1)- and beta(2)-adrenoceptors, respectively, was compared on sinoatrial beating rate, left atrial and ventricular contractile force in isolated tissues from Wistar rats. L-type Ca(2+)-current (I(Ca-L)) was assessed with whole-cell patch clamp. KEY RESULTS: Rolipram caused sinoatrial tachycardia. Cilostamide and rolipram did not enhance chronotropic potencies of (-)-noradrenaline and (-)-adrenaline. Rolipram but not cilostamide potentiated atrial and ventricular inotropic effects of (-)-noradrenaline. Cilostamide potentiated the ventricular effects of (-)-adrenaline but not of (-)-noradrenaline. Concurrent cilostamide + rolipram uncovered left atrial effects of (-)-adrenaline. Both rolipram and cilostamide augmented the (-)-noradrenaline (1 micromol x L(-1)) evoked increase in I(Ca-L). (-)-Adrenaline (10 micromol x L(-1)) increased I(Ca-L) only in the presence of cilostamide but not rolipram. CONCLUSIONS AND IMPLICATIONS: PDE4 blunts the beta(1)-adrenoceptor-mediated inotropic effects. PDE4 reduces basal sinoatrial rate in a compartment distinct from compartments controlled by beta(1)- and beta(2)-adrenoceptors. PDE3 and PDE4 jointly prevent left atrial beta(2)-adrenoceptor-mediated inotropy. Both PDE3 and PDE4 reduce I(Ca-L) responses through beta(1)-adrenoceptors but the PDE3 component is unrelated to inotropy. PDE3 blunts both ventricular inotropic and I(Ca-L) responses through beta(2)-adrenoceptors.
    [Abstract] [Full Text] [Related] [New Search]