Editors' ChoicePhysiology

Have You Heard About Levitra?

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Science Signaling  14 Feb 2012:
Vol. 5, Issue 211, pp. ec53
DOI: 10.1126/scisignal.2002955

The second messenger cGMP (cyclic guanosine monophosphate) activates cGMP-dependent protein kinases (Prkg) and is hydrolyzed by type 5 phosphodiesterases (Pde5). Pde5 inhibitors, such as vardenafil, are used to treat various conditions, including erectile dysfunction. Jaumann et al. found that Pde5 and Prkg1 were present in outer hair cells in mouse cochlea. After noise exposure, the extent of permanent hearing loss was greater in mice lacking Prkg1. In addition, these mice showed signs of damage to the outer hair cells, as indicated by lower-amplitude signals produced by functional outer hair cells. Furthermore, Prkg1-deficient mice showed greater numbers of outer hair cells with decreased surface abundance of Kcnq4, a potassium channel that mediates repolarization of these cells and whose surface abundance correlates with noise exposure. Rats pretreated with vardenafil before acoustic trauma showed recovery of outer hair cell responsiveness to pretrauma amplitudes and reduced thresholds required for auditory brainstem responses immediately after the acoustic trauma and after a recovery period (higher thresholds generally correlate with greater hearing loss). In addition, vardenafil prevented the loss of surface Kcnq4 from outer hair cells induced by acoustic trauma. Although these results suggest that Pde5 inhibitors could be used to treat or prevent noise-induced hearing loss, for which there is currently no effective treatment, Layman and Zuo note that some individuals on Pde5 inhibitors have experienced sudden, sometimes permanent, hearing loss.

M. Jaumann, J. Dettling, M. Gubelt, U. Zimmermann, A. Gerling, F. Paquet-Durand, S. Feil, S. Wolpert, C. Franz, K. Varakina, H. Xiong, N. Brandt, S. Kuhn, H.-S. Geisler, K. Rohbock, P. Ruth, J. Schlossmann, J. Hütter, P. Sandner, R. Feil, J. Engel, M. Knipper, L. Rüttiger, cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function. Nat. Med. 18, 252–259 (2012). [PubMed]

W. Layman, J. Zuo, An unheard benefit of phosphodiesterase inhibition. Nat. Med. 18, 206–207 (2012). [Online Journal]

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