title: Specific effects of n-3 fatty acids and 8-bromo-cGMP on the cyclic nucleotide phosphodiesterase activity in neonatal rat cardiac myocytes.
abstract: The authors have previously resolved four forms of cyclic nucleotide phosphodiesterase (PDE) in neonatal rat cultured cardiomyocytes by use of high-performance liquid chromatography (HPLC) and have shown that the response of the cGMP-stimulated PDE to the effector cGMP was markedly reduced as compared to that of the corresponding isoform present in the heart ventricle of adult rat (70% v 350%). When neonatal rat ventricular myocytes were grown in a medium enriched in docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), an increase of the basal level of cAMP and mainly cGMP was observed. The cGMP-PDE specific activity in the unfractionated cytosol of DHA-, EPA- or 8-bromo-cGMP-enriched cardiomyocytes was lower than that observed in control cells. Whereas the cAMP-PDE specific activity remained unchanged whatever the treatment used. At the same time, the response of the cGMP-stimulated PDE to cGMP was substantially increased in n-3 fatty acid-enriched cardiomyocytes and reached the same level as in the whole ventricle (340%). The treatment of neonatal cardiomyocytes with 8-bromo-cGMP also re-established the sensitivity of this cGMP-stimulated isozyme to cGMP (320%). These results suggest a common mechanism for polyunsaturated fatty acids and 8-bromo-cGMP in the regulation of the cGMP-stimulated PDE activity in cardiomyocytes from new-born rats.
authors.affiliation: Unité INSERM 352, Laboratoire de Chimie Biologique, Institut des Sciences Appliquées de Lyon, Villeurbanne, France.
authors.forename: M
authors.initials: M
authors.lastname: Picq
authors.forename: M
authors.initials: M
authors.lastname: Dubois
authors.forename: A
authors.initials: A
authors.lastname: Grynberg
authors.forename: M
authors.initials: M
authors.lastname: Lagarde
authors.forename: A F
authors.initials: AF
authors.lastname: Prigent
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005227:Fatty Acids / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D007700:Kinetics; D020105:Milrinone; D009206:Myocardium / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram
chemical_list: D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D011760:Pyrrolidinones; C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP; D020105:Milrinone; D020889:Rolipram