Pharmacological and biochemical study in ontogenetic aspect of 3'-5'-adenosinemonophosphate phosphodiesterases with low and high Km.

The ontogenetic development of 3',5'-AMP phosphatediesterase with low and high Km is studied in rat ileum and brain, and more specifically the changes in the kinetic parameters of the enzyme. Comparison of the Michaelis constants of the phosphodiesterase (PDE) in the ileum and brain of newborn and adult rats reveals a rise in their values in the ileum and a decrease in the brain. It may be assumed that the development of PDE with low Km in the ileum precedes that in the brain, which is directly related to the sequence in the postnatal development of the adaptational mechanisms to the environment in the young organism. In studies on the relation of PDE in the ileum and brain to some inhibitors (papaverine, theophylline, 6'-iodo-dihydropapaverine and 6'-bromo-dihydropapaverine) we established mosaic effects of these substances both with respect to the type of the enzyme and with respect to the age of the experimental animal. The results of our kinetic experiments showed that there was no difference in the type of inhibition and in the correlation of the inhibitory power of the drugs tested during ontogenesis. Probably no essential changes occur in the active centres of the enzymes during this period. The observed age changes in PDE with low and high Km condition the altered sensitivity of these enzymes to the inhibitors studied. The enzyme in the ileum of newborn animals--and organ with earlier functional maturation--is more sensitive to inhibitors. Conversely, PDE sensitivity in the brain increases during the ontogenesis.