The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D
| Autor: | J. Beleta, Guadalupe Mengod, Fumiaki Mori, J.M. Palacios, Andrea Porzionato, S. Pérez-Torres, R. De Caro, A. Gavaldà, Veronica Macchi |
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| Přispěvatelé: | Generalitat de Catalunya, Ministerio de Educación y Ciencia (España), European Commission |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty PDE4B Vomiting In situ hybridization Biology PDE4D Gene Expression Regulation Enzymologic Chemoreceptor trigger zone Cellular and Molecular Neuroscience Nucleus of the solitary tract Internal medicine Reflex medicine Cyclic AMP Solitary Nucleus Humans RNA Messenger Cellular localization In Situ Hybridization Aged Neurons Area postrema Solitary tract Phosphodiesterase Vagus Nerve Middle Aged Cyclic Nucleotide Phosphodiesterases Type 3 Cyclic Nucleotide Phosphodiesterases Type 4 Isoenzymes medicine.anatomical_structure Endocrinology In situ hybridization histochemistry Area Postrema Blood Vessels Female Brainstem Nucleus Neuroglia Dorsal vagal motor nucleus |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Phosphodiesterase 4 (PDE4) inhibitors, i.e. rolipram, are being extensively investigated as therapeutic agents in several diseases. Emesis is one of the most common side effects of PDE4 inhibitors. Given the fact that the area postrema is considered the chemoreceptor trigger zone for vomiting, the present study investigates the regional distribution and cellular localization of the four gene transcripts of the PDE4 subfamily (PDE4A, PDE4B, PDE4C and PDE4D) in human brainstem. In situ hybridization histochemistry was used to locate the mRNA distribution of the four PDE4 subfamilies in the area postrema and related nuclei of human postmortem brainstem. We have found that in the brainstem PDE4B and PDE4D mRNA expression is abundant and distributed not only in neuronal cells, but also in glial cells, and on blood vessels. The hybridization signals for PDE4B and PDE4D mRNAs in the area postrema were stronger than those in any other nuclei in the brainstem. They were also found in vomiting-related nuclei such as the nucleus of the solitary tract and the dorsal vagal motor nucleus. These findings suggest that cAMP signaling modification in the area postrema could mediate the emetic effects of PDE4 inhibitors in human brainstem. This work was supported by grants from Ministerio de Educación y Ciencia and Fondo Europeo de Desarrollo Regional (SAF2006-10243). F.M. was on sabbatical leave from Hirosaki University School of Medicine. S.P.-T. was recipient of a predoctoral fellowship from CIRIT (Generalitat de Catalunya). |
| Databáze: | OpenAIRE |
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