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The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D.

Abstract
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.
AuthorsF Mori, S Pérez-Torres, R De Caro, A Porzionato, V Macchi, J Beleta, A Gavaldà, J M Palacios, G Mengod
JournalJournal of chemical neuroanatomy (J Chem Neuroanat) Vol. 40 Issue 1 Pg. 36-42 (Sep 2010) ISSN: 1873-6300 [Electronic] Netherlands
PMID20347962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright2010 Elsevier B.V. All rights reserved.
Chemical References
  • Isoenzymes
  • RNA, Messenger
  • Cyclic AMP
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4A protein, human
  • PDE4B protein, human
  • PDE4C protein, human
  • PDE4D protein, human
Topics
  • Adult
  • Aged
  • Area Postrema (cytology, enzymology)
  • Blood Vessels (enzymology)
  • Cyclic AMP (metabolism)
  • Cyclic Nucleotide Phosphodiesterases, Type 3 (genetics)
  • Cyclic Nucleotide Phosphodiesterases, Type 4 (genetics)
  • Female
  • Gene Expression Regulation, Enzymologic (genetics)
  • Humans
  • In Situ Hybridization
  • Isoenzymes (genetics)
  • Male
  • Middle Aged
  • Neuroglia (cytology, enzymology)
  • Neurons (cytology, enzymology)
  • RNA, Messenger (metabolism)
  • Reflex (physiology)
  • Solitary Nucleus (cytology, enzymology)
  • Vagus Nerve (cytology, enzymology)
  • Vomiting (metabolism, physiopathology)

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