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 (</=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.
Montcouquiol
M
M
Department of Otolaryngology-Head, Neck, University of Virginia, School of Medicine, Charlottesville, Virginia 22908, USA.
Corwin
J T
JT
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D018069:Hair Cells, Vestibular / Q000166:cytology / Q000187:drug effects*; D007476:Ionophores / Q000494:pharmacology; D018942:Macrolides; D008985:Monensin / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1 / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects; D012444:Saccule and Utricle / Q000166:cytology / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007476:Ionophores; D018942:Macrolides; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D011994:Recombinant Proteins; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C040929:bafilomycin A1; D008985:Monensin; D017868:Cyclic AMP-Dependent Protein Kinases; D001973:Bromodeoxyuridine