In vitro induction of apoptosis or differentiation by dopamine in an immortalized olfactory neuronal cell line.
A new neuronal cell line was generated by transfection of rat olfactory epithelium with immortalizing recombinant oncogene E1A of adenovirus-2. The resulting 13.S.1.24 line of transformed cells expressed an antigenic phenotype of olfactory neuronal progenitors. Addition of dopamine to 13.S.1.24 cultures induced reduction of cell number within 2 days. Two hallmarks of apoptosis were detected in dopamine-treated cultures: internucleosomal DNA fragmentation and nuclear condensation. Dopamine did not alter the cell proliferation rate, as assessed by [3H]thymidine incorporation. Dopamine also stimulated differentiation of surviving 13.S.1.24 cells into bipolar olfactory marker protein-immunoreactive neurons. Time-dependency assessments over 1 week of treatment indicated that apoptosis and differentiation induced by dopamine were concomitant. Both apoptosis and differentiation triggered by dopamine were dose-dependent, half-maximal effects being obtained with approximately 10 microM dopamine. Mediation of both effects by dopaminergic D2 receptors was supported by several observations: active dopamine doses in micromolar ranges, quinpirole agonism and eticlopride antagonism, D2-characteristic rank order of potency among the three agonists tested, and specific binding of a selective D2-like radioligand to 13.S.1.24 cells. The present data altogether indicated that dopamine commits immortalized olfactory neuronal cells in vitro either to apoptosis or to olfactory-like differentiation via D2 dopaminergic receptors.
Coronas
V
V
Neurosciences et Systèmes Sensoriels, Université Claude Bernard-Lyon I, Villeurbanne, France.
Féron
F
F
Hen
R
R
Sicard
G
G
Jourdan
F
F
Moyse
E
E
D000256:Adenoviridae; D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D053938:DNA Fragmentation; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009831:Olfactory Mucosa / Q000294:innervation*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis; D012457:Salicylamides / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
D017500:Adenovirus E1A Proteins; D018492:Dopamine Antagonists; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D011994:Recombinant Proteins; D012457:Salicylamides; D019257:Quinpirole; C045989:eticlopride; D013936:Thymidine; D004298:Dopamine