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

Degerman, Eva LU ; in 't Zandt, Rene LU ; Pålbrink, Annki; Eliasson, Lena LU ; Cayé-Thomasen, Per and Magnusson, Måns LU (2016) In Acta Oto-Laryngologica p.1-8
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
Aquaporin2, cilostamide, cochlea, Ménière’s disease, rolipram, sildenafil
in
Acta Oto-Laryngologica
pages
8 pages
publisher
Taylor & Francis
external identifiers
  • Scopus:84981717811
ISSN
0001-6489
DOI
10.1080/00016489.2016.1211320
language
English
LU publication?
yes
id
2bcc2342-9526-4f49-9833-2da29ac9e351
date added to LUP
2016-09-20 15:10:36
date last changed
2016-11-03 14:33:40
@misc{2bcc2342-9526-4f49-9833-2da29ac9e351,
  abstract     = {<p>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.</p>},
  author       = {Degerman, Eva and in 't Zandt, Rene and Pålbrink, Annki and Eliasson, Lena and Cayé-Thomasen, Per and Magnusson, Måns},
  issn         = {0001-6489},
  keyword      = {Aquaporin2,cilostamide,cochlea,Ménière’s disease,rolipram,sildenafil},
  language     = {eng},
  month        = {08},
  pages        = {1--8},
  publisher    = {ARRAY(0x8598c08)},
  series       = {Acta Oto-Laryngologica},
  title        = {Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI},
  url          = {http://dx.doi.org/10.1080/00016489.2016.1211320},
  year         = {2016},
}