title: PDE2 activity differs in right and left rat ventricular myocardium and differentially regulates β2 adrenoceptor-mediated effects.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology A, University of Murcia, 30100 Murcia, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Soler
authors.affiliation: Department of Biochemistry and Molecular Biology A, University of Murcia, 30100 Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernández-Belda
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Pérez-Schindler
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
authors.affiliation: Unit of Radiopharmacy, University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
authors.forename: Teodomiro
authors.initials: T
authors.lastname: Fuente
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain jehernca@um.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Hernandez-Cascales
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; C010192:9-(2-hydroxy-3-nonyl)adenine; C049763:CGP 20712A; D000242:Cyclic AMP; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D000225:Adenine; D000420:Albuterol
keywords: PDE2 activity; cAMP levels; inotropy; interventricular differences; β2 adrenoceptor