Differential distribution of PDE4D splice variant mRNAs in rat brain suggests association with specific pathways and presynaptical localization

Authors

  • Xavier Miró,

    1. Department of Molecular Genetics, Instituto de Biología Molecular de Barcelona, CID-CSIC, E-08034 Barcelona, Spain
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  • Silvia Pérez-Torres,

    1. Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona, CSIC (IDIBAPS), Barcelona E-08036, Spain
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  • Pere Puigdomènech,

    1. Department of Molecular Genetics, Instituto de Biología Molecular de Barcelona, CID-CSIC, E-08034 Barcelona, Spain
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  • José M. Palacios,

    1. Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona, CSIC (IDIBAPS), Barcelona E-08036, Spain
    Current affiliation:
    1. Research Center, Almirall Prodesfarma S.A., Cardener 68-74, E-08024 Barcelona, Spain
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  • Guadalupe Mengod

    Corresponding author
    1. Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona, CSIC (IDIBAPS), Barcelona E-08036, Spain
    • Department of Neurochemistry IIBB-CSIC (IDIBAPS), Rosselló 161 6 floor, Barcelona 08036, Spain
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Abstract

cAMP plays an important role as a second-messenger molecule controlling multiple cellular processes. Its hydrolysis provides an important mechanism by which cAMP levels are regulated. This is performed by a large multigene family of cyclic nucleotide phosphodiesterases (PDEs). Members of the PDE4 enzyme family are selectively inhibited by rolipram. Five different mRNA splice forms for PDE4D have been isolated. Here, we analyzed the regional distribution of the mRNAs coding for the splice variants PDE4D1, PDE4D2, PDE4D3, PDE4D4, and PDE4D5 in the rat brain by in situ hybridization histochemistry using specific radiolabeled oligonucleotides. We found that all five splice variants showed a distinct distribution pattern and, in some cases, in association with specific brain pathways. The most relevant differences were in hippocampal formation, medial habenula, basal ganglia, and area postrema, at both the regional and cellular level. The dorsal and median raphe nuclei exclusively contained PDE4D2 mRNA transcripts, probably located on serotonergic cells. PDE4D1 mRNA was expressed in some white matter cells. PDE4D1 and PDE4D2 mRNA splice forms presented a similar distribution in the area postrema, whereas for PDE4D4 and PDE4D5 the cellular distribution presented a complementary pattern. The differential expression of PDE4D mRNA splice variants in the area postrema is consistent with their possible involvement in emesis control and suggests new molecular targets for a more selective drug design. Synapse 45:259–269, 2002. © 2002 Wiley-Liss, Inc.

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