The actions of retinoids on cellular growth correlate with their actions on gap junctional communication.
Retinoic acid (a possible morphogen), its biological precursor retinol, and certain synthetic derivatives of retinol profoundly change junctional intercellular communication and growth (saturation density) in 10T 1/2 and 3T3 cells and in their transformed counterparts. The changes correlate: growth decreases as the steady-state junctional permeability rises, and growth increases as that permeability falls. Retinoic acid and retinol exert quite different steady-state actions on communication at noncytotoxic concentrations in the normal cells: retinoic acid inhibits communication at 10(-10)-10(-9) M and enhances at 10(-9)-10(-7) M, whereas retinol only enhances (10(-8)-10(-6) M). In v-mos-transformed cells the enhancement is altogether lacking. But regardless of the retinoid or cell type, all growth responses show essentially the same dependence on junctional permeability. This is the expected behavior if the cell-to-cell channels of gap junctions disseminate growth-regulating signals through cell populations.
Mehta
P P
PP
Department of Physiology and Biophysics, University of Miami School of Medicine, Florida 33101.
Bertram
J S
JS
Loewenstein
W R
WR
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002461:Cell Line, Transformed; D002463:Cell Membrane Permeability / Q000187:drug effects; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D007365:Intercellular Junctions / Q000187:drug effects* / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D000084562:Retinyl Esters; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology
D001565:Benzoates; D004224:Diterpenes; D012176:Retinoids; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid