DIFFERENTIAL CELLULAR-PATTERN OF GENE-EXPRESSION FOR 2 DISTINCT CGMP-INHIBITED CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES IN DEVELOPING AND MATURE RAT-BRAIN

Cyclic GMP-inhibited phosphodiesterases are characterized by sensitivi ty of cAMP hydrolysis to inhibition by cGMP. This phosphodiesterase fa mily contains at least two different isoforms (PDE3A and PDE3B) encode d by distinct genes and serving tissue-specific roles in regulation of lipolysis, glycogenolysis, myocardial contractility, and smooth muscl e relaxation. Our previous work indicated an abundance of these two ph osphodiesterase messenger RNAs in the embryonic rat brain, and therefo re, to elucidate the potential functions of these enzymes in brain dev elopment as well as in mature brain function, the present study mapped cellular patterns of gene expression for these two enzymes from embry onic day 15 to adulthood using in situ hybridization histochemistry. P hosphodiesterase 3B isoform messenger RNA is uniformly expressed in ge rminal neuroepithelium and mature neurons, with distribution generally reflecting cell density. Phosphodiesterase isoform 3A messenger RNA, in contrast, demonstrates striking spatiotemporal specificity of expre ssion, with three distinct patterns being evident. Firstly, this mRNA is highly abundant in both primary and secondary neuroepithelial germi nal zones. Secondly, during early postnatal development PDE3A mRNA is transiently but highly expressed in neurons localized in basal forebra in, deep cerebellar, pontine, interpeduncular and a variety of thalami c, midbrain and brainstem nuclei. Thirdly, PDE3A mRNA is focally expre ssed in isolated large striatal and hippocampal neurons from the perin atal period without attenuation into adulthood. In summary, two cGMP-i nhibited phosphodiesterase isoforms show distinctive patterns of gene expression in brain: PDE3B gene expression is uniform without evidence of system specificity or developmental stage specificity, suggesting that this isoform has a constitutive role in neuroepithelial metabolis m, while PDE3B gene expression demonstrates a high level of spatiotemp oral heterogeneity, suggesting that this isoform subserves a variety o f developmental stage-specific and system-specific functions.