PDE2 activity differs in right and left rat ventricular myocardium and differentially regulates β2 adrenoceptor-mediated effects
| Autor: | Christoph Handschin, Jesús Hernández-Cascales, Francisco Fernandez-Belda, Joaquín Pérez-Schindler, Teodomiro Fuente, Fernando Soler |
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| Rok vydání: | 2014 |
| Předmět: |
Inotrope
Agonist Cardiac function curve medicine.medical_specialty Adrenergic receptor Phosphodiesterase Inhibitors medicine.drug_class Heart Ventricles Adrenergic beta-Antagonists In Vitro Techniques Biology General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Contractility Internal medicine Cyclic AMP medicine Animals Albuterol RNA Messenger Adrenergic beta-2 Receptor Agonists Original Research Messenger RNA Adenine Myocardium fungi Imidazoles Antagonist Cyclic Nucleotide Phosphodiesterases Type 2 Myocardial Contraction Rats Endocrinology Receptors Adrenergic beta-2 EHNA medicine.drug |
| Zdroj: | Experimental Biology and Medicine. 240:1205-1213 |
| ISSN: | 1535-3699 1535-3702 |
| Popis: | The important regulator of cardiac function, cAMP, is hydrolyzed by different cyclic nucleotide phosphodiesterases (PDEs), whose expression and activity are not uniform throughout the heart. Of these enzymes, PDE2 shapes β1 adrenoceptor-dependent cardiac cAMP signaling, both in the right and left ventricular myocardium, but its role in regulating β2 adrenoceptor-mediated responses is less well known. Our aim was to investigate possible differences in PDE2 transcription and activity between right (RV) and left (LV) rat ventricular myocardium, as well as its role in regulating β2 adrenoceptor effects. The free walls of the RV and the LV were obtained from Sprague–Dawley rat hearts. Relative mRNA for PDE2 (quantified by qPCR) and PDE2 activity (evaluated by a colorimetric procedure and using the PDE2 inhibitor EHNA) were determined in RV and LV. Also, β2 adrenoceptor-mediated effects (β2-adrenoceptor agonist salbutamol + β1 adrenoceptor antagonist CGP-20712A) on contractility and cAMP concentrations, in the absence or presence of EHNA, were studied in the RV and LV. PDE2 transcript levels were less abundant in RV than in LV and the contribution of PDE2 to the total PDE activity was around 25% lower in the microsomal fraction of the RV compared with the LV. β2 adrenoceptor activation increased inotropy and cAMP levels in the LV when measured in the presence of EHNA, but no such effects were observed in the RV, either in the presence or absence of EHNA. These results indicate interventricular differences in PDE2 transcript and activity levels, which may distinctly regulate β2 adrenoceptor-mediated contractility and cAMP concentrations in the RV and in the LV of the rat heart. |
| Databáze: | OpenAIRE |
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