Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI

Research output: Contribution to journalArticle

Abstract

Conclusion: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear. Objective: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling. Method: To evaluate the role of PDE3, 4, and 5 and associated cAMP and cGMP pools in inner ear function, the effect of cilostamide (PDE3 inhibitor), rolipram (PDE4 inhibitor), and sildenafil (PDE5 inhibitor), administrated via mini-osmotic pumps, on mouse inner ear fluid homeostasis was evaluated using 9.4T in vivo MRI in combination with intraperitoneally administered Gadolinium contrast. Also, using human saccule as a model, the expression of PDEs and related signaling molecules and targets was studied using immunohistochemistry. Results: PDE3, PDE4, as well as PDE5 inhibitors resulted in the development of endolymphatic hydrops. Furthermore, PDE3B, PDE4D, and some related signaling components were shown to be expressed in the human saccule.

Details

Authors
Organisations
External organisations
  • Copenhagen University Hospital
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Otorhinolaryngology

Keywords

  • Aquaporin2, cilostamide, cochlea, Ménière’s disease, rolipram, sildenafil
Original languageEnglish
Pages (from-to)8-15
Number of pages8
JournalActa Oto-Laryngologica
Volume137
Issue number1
Early online date2016 Aug 12
StatePublished - 2017
Peer-reviewedYes