The Journal of Neuroscience, February 1, 2001, 21(3):974-982
Brief Treatments with Forskolin Enhance S-Phase Entry in Balance
Epithelia from the Ears of Rats
Mireille
Montcouquiol and
Jeffrey T.
Corwin
Department of Otolaryngology-Head, Neck, and Surgery and
Department of Neuroscience, University of Virginia, School of
Medicine, Charlottesville, Virginia 22908
In the ears of mammals, hair cell loss results in permanent hearing
and balance deficits, whereas in fish, amphibians, and birds, the
production of replacement hair cells can restore those modalities. In
avian ears, continuous exposures to forskolin trigger cell
proliferation and the regeneration of hair cells, so we investigated the effect of forskolin on sensory epithelia cultured from the ears of
mammals. Continuous 72 hr exposures to forskolin failed to induce
proliferation in neonatal rat utricles, but brief (
1 hr) exposures to
forskolin or Br-cAMP did. Proliferation occurred only in media that
contained serum. Forskolin also augmented the mitogenic effects of
glial growth factor 2. The S-phase entry induced by forskolin was
blocked by monensin and bafilomycin, two compounds that can inhibit the
recycling of membrane receptors. The results are consistent with the
hypothesis that in mammalian vestibular epithelia elevated cAMP induces
S-phase entry by increasing the number of growth factor receptors at
the plasma membrane.
Key words:
regeneration; hair cells; cell proliferation; hearing; cAMP; receptor recycling
Copyright © 2001 Society for Neuroscience 0270-6474/01/213974-09$05.00/0
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