Cyclic AMP-dependent protein kinase (PKA) gene expression is developmentally regulated in fetal lung.
We characterized the ontogeny of cAMP-dependent protein kinase (PKA) enzymatic 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 lung, 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 and lowest in the adult lung. However, RII alpha mRNA levels were similar in the 18-day, 20-day and newborn lungs. Dexamethasone treatment of fetal lung explants resulted in a small decrease in RI alpha mRNA levels 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 activity at the time of type II alveolar cell differentiation, presumably in preparation for air breathing. The absence of an effect of glucocorticoid on PKA activity suggests that glucocorticoids are not responsible for the increase in PKA activity which accompanies this critical time in lung maturation.
Acarregui
M J
MJ
Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242, USA. macarreg@peds-po.peds.uiowa.edu
Brown
J J
JJ
Penisten
S T
ST
D000818:Animals; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517836:Prkar1a protein, rat; C517822:Prkar2a protein, rat; D012333:RNA, Messenger; D003907:Dexamethasone; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases