SEROTONIN UPTAKE, STORAGE, AND SYNTHESIS IN AN IMMORTALIZED COMMITTED CELL-LINE DERIVED FROM MOUSE TERATOCARCINOMA

We report the isolation and characterization of a serotoninergic cell line, 1C11, derived from a mouse teratocarcinoma. The clone 1C11 was immortalized through the expression of the simian virus 40 oncogenes. 1C11 presents two states: an immature epithelial-like state (1C11 precursor) and a more differentiated state (1C11*). After induction by dibutyryl cyclic AMP and cyclohexanecarboxylic acid, almost 100% of the 1C11* cells continue to divide and have acquired a neural-like phenotype. 1C11* cells coexpress several neural markers, such as synaptophysin (the membrane constituent of synaptic vesicles), the neuropeptide [Met5]enkephalin, and the neurotransmitter serotonin. 1C11* cells store endogenous serotonin and are able to synthesize serotonin from L-tryptophan and to catabolize it by monoamine oxidase B. Moreover, the cells take up serotonin by a carrier-mediated mechanism very similar to that of serotoninergic neurons. The expression of the simian virus 40 oncogenes, which promoted immortalization does not therefore prevent further differentiation. This inducible cell line constitutes a valuable model for cellular and molecular studies concerning the physiology and the pharmacological modulation of the serotoninergic phenotype.