Brief treatments with forskolin enhance S-phase entry in balance epithelia from the ears of rats

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 (less than or equal to1 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.