DEVELOPMENTAL DIFFERENCES IN DISTRIBUTION OF CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE ISOFORMS IN CARDIOMYOCYTES AND THE VENTRICULAR TISSUE FROMNEWBORN AND ADULT-RATS

We characterized cyclic nucleotide phosphodiesterase (PDE) activities in neonatal rat cardiomyocytes and in whole ventricle from newborn and adult rats, to determine whether cyclic nucleotide hydrolytic activit ies might be influenced by the developmental stage of the animal or by cell isolation and culture procedures, Using anion-exchange high-perf ormance liquid chromatography (HPLC), we obtained four soluble PDE act ivities from adult rat ventricle. Peak 1, a cyclic GMP-specific PDE wa s stimulated by Ca2+/calmodulin; peak 2 hydrolyzed cyclic AMP and cycl ic GMP, the addition of cyclic GMP stimulating the hydrolysis of cycli c AMP. Peaks 3 and 4 selectively hydrolyzed cyclic AMP, peak 3 being v ery sensitive to inhibition by rolipram and peak 4 consisting of two d ifferent enzyme activities, one inhibited by cyclic GMP (peak 4b) and the other inhibited by rolipram (peak 4a). In cardiomyocytes and whole ventricle from newborn rats, the response of the two cyclic GMP-sensi tive PDE isoforms (cyclic GMP-stimulated and cyclic GMP-inhibited PDE) to the effector cyclic GMP was markedly reduced as compared with that of the corresponding isoforms (peaks 2 and 4b) present in the heart v entricle of adult rats, The other peaks were analogous to peaks 1, 3, and 4a of the whole ventricle. The profile of PDE activities in nonmyo cardial cells did not differ from that of myocytes, Therefore, the lac k of cyclic GMP effects was not due to culture conditions, Differences in PDE activities observed between cardiomyocytes from newborn rats a nd ventricle from adult rats might be age dependent.