Ontogeny of rolipram-sensitive, low-K(m), cyclic AMP-specific phosphodiesterase in rat brain.
The postnatal development of rolipram-sensitive, low-K(m), cyclic AMP-specific phosphodiesterase (PDE4) was investigated in discrete regions of rat brain using a PDE4 activity assay and immunoblot analyses with K116, a PDE4 antibody. The Vmax for cyclic AMP hydrolysis by PDE4 was lower at birth when compared to adult levels in cerebral cortex, cerebellum, and neostriatum. K(m) values for cyclic AMP hydrolysis by PDE4, in contrast, did not change throughout the observed period in any brain region tested. The developmental patterns for PDE4 were significantly different among the examined brain regions. PDE4 activity in olfactory bulb and hippocampus also was found to be lower at birth in comparison to adult levels. Immunoblot analyses showed that developmental patterns of PDE4 were significantly different for the various subtypes, and also varied substantially across brain regions. The results suggest that PDE4 might be differentially regulated by different ontogenetic events.
Zhang
K
K
Department of Pharmacology and Therapeutics, Louisiana State University School of Medicine, Shreveport 71130, USA. kz@mclean.harvard.edu
Farooqui
S M
SM
O'Donnell
J M
JM
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005260:Female; D006868:Hydrolysis; D015151:Immunoblotting; D007700:Kinetics; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram; D014018:Tissue Distribution