Ontogenetic changes in levels of phosphodiesterase for adenosine 3':5'-monophosphate and glucosine 3':5'-monophosphate in the lung, brain and heart from guinea pigs.

Changes in tissue levels of the low Km phosphodiesterase for adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclc GMP) in the lung, liver, heart and brain from developing guinea pigs were studied. It was found that the contents of the soluble (cytosol) phosphodiesterase for both cyclic AMP and cyclic GMP were higher in the lung from the fetus than from the neonate and adult. The ontogenetic changes seen in the liver were qualitatively similar to thos in the lung with respect to cyclic GMP hydrolysis, while a reversed pattern of change was noted in the brain. The level of cyclic AMP phosphodiesterase was highest in the fetal heart. Throughout the fetal stage, the levels of the enzyme for cyclic GMP hydrolysis were higher than those for cyclic AMP in the lung. At or around birth, a reversal in the relative levels of the two enzymes took place; two days after birth, the level of the enzyme for cyclic AMP was 2-3times higher than thos for cyclic GMP. Kinetic analysis showed that phohphodiesterases from extracts of the lung from all developmental stages of guinea pigs had the same Km (2.6 muM) for cyclic AMP and the same Km (6.6 muM) for cyclic GMP. The relative values of V, based on assays using the same amount of enzyme protein, in decreasing order, were fetus greater than neonate greater than adult. The present findings suggest that metabolism of the two cyclic nucleotides may be closely related to developmental processes of the tissues. Moreover, the actions involving cyclic GMP may be more predominent in the fetal lung and adult brain.