CYCLIC-AMP-DEPENDENT PROTEIN-KINASE (PKA) GENE-EXPRESSION IS DEVELOPMENTALLY-REGULATED IN FETAL LUNG

We characterized the ontogeny of CAMP-dependent protein kinase (PKA) e nzymatic activity and PKA subunit mRNA expression in developing lung. The lungs of fetal Sprague-Dawley rat pups were removed after 16, 18, or 20 days of gestation and at term. PKA activity was greatest in the 18- and 20-day gestation lungs. Tissue CAMP levels were lowest in the 16-day lungs and increased with lung maturity. We were able to detect only low levels of mRNA for the C beta subunit of PKA by northern blot analysis of total lung RNA and we were able to detect mRNA for the RI beta and RII beta subunits only by RT-PCR. Therefore, we limited our analysis of PKA subunit mRNA levels to those for C alpha, RI alpha and RII alpha. The mRNA levels for C alpha, were highest in the 16-day lu ng, decreased at 18 and 20 days, were lower in the newborn and lowest in the adult lung. RI alpha mRNA levels were also highest at 16 days a nd lowest in the adult lung. However, RII alpha mRNA levels were simil ar in the is-day, 20-day and newborn lungs. Dexamethasone treatment of fetal lung explants resulted in a small decrease in RI alpha mRNA lev els but was not associated with a change in PKA activity. We conclude that PKA activity and PKA subunit mRNA expression are developmentally regulated in fetal lung. Such regulation results in optimal PKA activi ty at the time of type II alveolar cell differentiation, presumably in preparation for air breathing. The absence of an effect of glucocorti coid on PKA activity suggests that glucocorticoids are not responsible for the increase in PKA activity which accompanies this critical time in lung maturation. (C) 1998 Elsevier Science B.V.