Inhibition of the adrenergic phenotype in cultured neural crest cells by norepinephrine uptake inhibitors.
Tricyclic antidepressants in combination with in vitro clonal analysis of quail neural crest cells were used to examine the role the norepinephrine uptake mechanism might play in the development of adrenergic neural crest derivatives. Norepinephrine (NE) uptake inhibitors blocked expression of the adrenergic phenotype by neural crest cells. The degree of inhibition of phenotypic expression correlated with the potency and specificity of the uptake inhibitors. The drugs acted during the early phase of in vitro development, i.e., several days before overt expression of the adrenergic phenotype in clonal culture. They were nontoxic, and a chronic exposure of the cells to NE uptake inhibitors was necessary to cause an effect. These observations suggest that norepinephrine and possibly related neurotransmitters play a direct or indirect role in the expression of the adrenergic phenotype by neural crest cells and that tricyclic antidepressants may affect neurogenesis during sensitive stages of embryonic development. The data may reflect in vivo mechanisms, since there are neurotransmitters present in the migratory pathway of presumptive sympathetic neurons and the norepinephrine uptake system is expressed in the embryo by these cells before they synthesize and accumulate catecholamines.
Sieber-Blum
M
M
Department of Anatomy and Cellular Biology, Medical College of Wisconsin, Milwaukee 53226.
D000320:Adrenergic Fibers / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology; D003370:Coturnix / Q000196:embryology; D003891:Desipramine / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008454:Mazindol / Q000494:pharmacology; D009432:Neural Crest / Q000166:cytology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014179:Neurotransmitter Uptake Inhibitors; D015283:Citalopram; D008012:Lidocaine; D008454:Mazindol; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D003891:Desipramine; D002746:Chlorpromazine; D009638:Norepinephrine