Differential distribution of cAMP-specific phosphodiesterase 7A mRNA in rat brain and peripheral organs.
We investigated the regional distribution and cellular localization of mRNA coding for the cAMP-specific phosphodiesterase 7A (PDE7A) in rat brain and several peripheral organs by in situ hybridization histochemistry. The regional expression of two splice variants, PDE7A1 and PDE7A2, was examined by RT-PCR using RNA extracted from several brain regions. PDE7A mRNA was found to be widely distributed in rat brain in both neuronal and nonneuronal cell populations. The highest levels of hybridization were observed in the olfactory bulb, olfactory tubercle, hippocampus, cerebellum, medial habenula nucleus, pineal gland, area postrema, and choroid plexus. Positive hybridization signals were also detected in other areas, such as raphe nuclei, temporal and entorhinal cortex, pontine nuclei, and some cranial nerve motor nuclei. Both mRNA splice forms were differentially distributed in several areas of the brain with the striatum expressing only PDE7A1 and the olfactory bulb and spinal cord expressing PDE7A2 exclusively. In peripheral organs the highest levels of PDE7A hybridization were seen in kidney medulla, although testis, liver, adrenal glands, thymus, and spleen also presented high hybridization signal. These results are consistent with PDE7A being involved in the regulation of cAMP signaling in many brain functions. The consistent colocalization with PDE4 mRNAs suggests that PDE7A could have an effect on memory, depression, and emesis. The results offer clear anatomical and functional systems in which to investigate future specific PDE7 inhibitors.
Miró
X
X
Department of Molecular Genetics, Instituto de Biología Molecular de Barcelona, CID-CSIC, Barcelona, Spain.
Pérez-Torres
S
S
Palacios
J M
JM
Puigdomènech
P
P
Mengod
G
G
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; D007668:Kidney / Q000033:anatomy & histology / Q000201:enzymology; D008297:Male; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D014781:Viscera / Q000201:enzymology*
D020033:Protein Isoforms; D012333:RNA, Messenger; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517461:Pde7a protein, rat