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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hernandez, Jesus Vargas, Maria Luisa Kaumann, Alberto J. |
| Description | Author Affiliation: Vargas ML ( Department of Pharmacology, University of Murcia, Murcia, Spain.) |
| Abstract | 1.--The cardiostimulant effects of CGP12177, mediated through a beta(1)-adrenoceptor site with low affinity for (-)-propranolol, are potentiated by the nonselective PDE inhibitor IBMX but the role of PDE isoenzymes is unknown. We studied the effects of the PDE3-selective inhibitor cilostamide (300 nM) and PDE4-selective inhibitor rolipram (1 microM) on the positive inotropic and cyclic AMP-enhancing effects of CGP12177 and noradrenaline in right ventricular strips of rat. 2.--CGP12177 (under (-)-propranolol 200 nM) only increased contractile force in the presence of either cilostamide or rolipram with -logEC(50)M 6.7 (E(max)=23% over basal) and 7.1 (E(max)=50%) respectively. The combination of cilostamide and rolipram caused CGP12177 to enhance contractile force with -logEC(50)M=7.7 and E(max)=178%. 3.--The positive inotropic effects of noradrenaline (-logEC(50)M=6.9) were potentiated by rolipram (-logEC(50)M=7.4) but not by cilostamide (-logEC(50)M=7.0). 4.--In the presence of rolipram and (-)-propranolol, noradrenaline (2 microM) and CGP12177 (10 microM) produced matching inotropic effects but failed to increase cyclic AMP levels. 20 microM (-)-noradrenaline increased cyclic AMP levels, a response further enhanced by rolipram. 5.--Both PDE3 and PDE4 of rat ventricle appear to hydrolyse cyclic AMP generated through the low-affinity beta(1)-adrenoceptor site, thereby preventing inotropic responses of CGP12177. When (-)-noradrenaline interacts with the beta(1)-adrenoceptor, the generated cyclic AMP is hydrolysed only by PDE4, thereby reducing cardiostimulation. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 147 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2006-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | 3',5'-Cyclic-AMP Phosphodiesterases Physiology Adrenergic Beta-1 Receptor Agonists Cyclic AMP Metabolism Myocardial Contraction Drug Effects Norepinephrine Pharmacology Propanolamines Antagonists & Inhibitors Animals Cyclic Nucleotide Phosphodiesterases, Type 3 Cyclic Nucleotide Phosphodiesterases, Type 4 Heart Ventricles In Vitro Techniques Myocardium Quinolones Rats, Sprague-Dawley Rolipram Stimulation, Chemical Ventricular Function |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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